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Lymphocyte-predominant Hodgkin lymphoma (LPHL), according to the Revised European-American Lymphoma classification, was considered on a retrospective basis as a specific clinical entity with a large majority of patients at clinical stage (CS) IA or IIA. Of the 500 patients with CS IA/IIA Hodgkin lymphoma (HL) prospectively treated between 1981 and 1996 by one or 3 courses of anthracycline-based chemotherapies combined with high-dose extended irradiation, disease in 42 patients was reclassified as LPHL. These 42 patients, none of whom had mediastinal involvement (MI), were compared with the 458 patients with classical HL (cHL), 144 without MI and 314 with MI. Surprisingly, the male-female ratio, age, first site involved, hemoglobin level, lymphocyte count, and sedimentation rate of patients with LPHL and cHL without MI were identical and significantly different from those of patients with cHL with MI. Moreover, 15-year HL mortality rates were similarly low in patients with LPHL (2.4%) and cHL without MI (0.7%). Overall survival rates were also similar (86% and 82%) and as high as 100% and 95% in patients treated before the age of 40 years. This study demonstrated that LPHL and cHL without MI shared the same presenting characteristics and the same excellent long-term prognosis after a brief anthracycline-based chemotherapy plus high-dose extended irradiation.

From 1990 to 1996, a total of 386 adult patients with early/intermediate Hodgkin disease (HD) were randomly assigned to receive 3 cycles of adriamycin, bleomycin, vinblastine, dacarbazine (an alkylating agent), and methylprednisolone (ABVDm, arm A) or epirubicin, bleomycin, vinblastine, methotrexate, and methylprednisolone (EBVMm, arm E), a combination without alkylating agent. Responding patients received extended field radiation therapy (RT). Postchemotherapy complete remission and 10-year freedom from progression rates were higher in arm A (79.5% and 91.4%) than in arm E (70.4%, P =.04, and 80%, P <.002). HD mortality (HDM), treatment-related mortality (TRM), and overall survival (OS) were similar in both arms (A, 2.1%, 7.5%, and 90.4%; B, 3.9%, 5.5%, and 90.3%). However TRM and OS rates were lower in patients aged 40 years or older (P <.005), reflecting the increasing incidence of background fatal events with increasing age. Finally, event-free survival (EFS) was higher in arm A (84.6%) than in arm E (74.9%, P <.02). In patients aged younger than 40 years in arm A (74%), 10-year EFS and OS rates were 88.9% and 95.4% with HDM and TRM rates as low as 0.7% and 3%. Three courses of ABVDm plus RT are the best available option for treating early or intermediate HD.

Between 1972 and 1988, 869 adult patients received MOPP (mechlorethamine, vincristine, procarbazine and prednisone; 462 patients) or ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine; 373 patients) and subsequent high-dose irradiation for Hodgkin's disease. Nine patients developed a leukaemia after MOPP and four after ABVD; 11 patients were diagnosed as acute non-lymphoblastic leukaemia (ANLL) and two as acute lymphoblastic leukaemia (ALL). Both cases of ALL were observed after ABVD and were associated with a 11q23 translocation. The 15-year actuarial risk of secondary leukaemia was 2.4% for the whole group of patients, 3.4% after MOPP and 1.3% after ABVD. For the MOPP subgroup, the risk of leukaemia was significantly associated with the extent of irradiation: 2.4% for limited irradiation and 13.9% for extended irradiation (P < 0.001). For the ABVD subgroup, this risk remained low (1.3%) whatever the type of irradiation. Concerning ANLL, the MOPP regimen was significantly associated with a higher risk: 3.4% versus 0.7% for ABVD (P

Purpose: Primary thyroid lymphoma (PTL) is a rare disease. Few patients are reported in the literature. We report eight new cases of PTL with long-term follow-up., Results: The clinical presentation was usually an enlarging neck mass squeezing surrounding structures. The diagnosis was established after thyroidectomy with histopathologic and immunohistochemical studies. Histology showed infiltrates of chronic lymphocytic thyroiditis in all cases. Three patients had thyroid lymphoma arising from mucosa-associated lymphoid tissue. One patient died postoperatively. The other seven were treated with combined chemotherapy and radiotherapy. They were still in remission after a 6-year follow-up., Conclusion: Diagnosis of PTL should be suspected when there is a recent thyroid enlargement. Surgery associated with chemotherapy and radiation gave good results in our study with long-term follow-up, though surgery was not always recommended in previous reports.

Severe T-cell immunodeficiency after solid organ or bone marrow transplantation may result in the uncontrolled outgrowth of latently Epstein-Barr virus-infected B cells, leading to B-lymphoproliferative disorder (BLPD). Given the potentially important pathogenic role of IL-6 in BLPD, it was tested whether the in vivo neutralization of IL-6 by a monoclonal anti-IL-6 antibody could contribute to the control of BLPD. Safety and efficacy were assessed in 12 recipients of transplanted organs who had BLPD refractory to the reduction of immunosuppression over 8 days. Five patients received 0.4 mg/kg per day. The next 7 patients received 0.8 mg/kg per day. Treatment was scheduled to last 15 days. It was completed in 10 patients, and in the other 2 patients was discontinued early (days 10 and 13, respectively) because of disease progression. Treatment tolerance was good, and no major side effects were observed. High C-reactive protein levels were found in 9 patients before treatment but were normalized under treatment in all patients, demonstrating efficient IL-6 neutralization. Complete remission (CR) was observed in 5 patients and partial remission (PR) in 3 patients. Relapse was observed in 1 of these 8 patients in whom remission was observed. This relapse was unresponsive to treatment. Disease was stable in 1 patient, but it progressed in 3 patients. Seven patients are alive and well. Two patients died because of disease progression, and 3 patients died while in CR (chronic rejection in 2 patients and BLPD sequelae in 1 patient). These data suggest that the anti-IL-6 antibody is safe and should be further explored in the treatment of BLPD.

The clinical activity of rituximab, a chimeric monoclonal antibody which binds to the CD20 antigen, was evaluated as a single first-line therapy for patients with follicular non-Hodgkin lymphoma (NHL). Fifty patients with follicular CD20(+) NHL and a low tumor burden were analyzed for clinical and molecular responses. They received 4 weekly infusions of rituximab at a dose of 375 mg/m(2). The response rate a month after treatment (day 50) was 36 of 49 (73%), with 10 patients in complete remission, 3 patients in complete remission/unconfirmed, and 23 patients in partial remission. Ten patients had stable disease, and the disease progressed in 3 patients. One of 13 (8%) patients in complete remission, 9 of 23 (39%) patients in partial remission, and 5 of 10 (50%) patients with stable disease exhibited disease progression during the first year. Within the study population, 32 patients were initially informative for polymerase chain reaction (PCR) data on bcl-2-J(H) rearrangement. On day 50, 17 of 30 patients (57%) were negative for bcl-2-J(H) rearrangement in peripheral blood, and 9 of 29 (31%) were negative in bone marrow; a significant association was observed between molecular and clinical responses (P <.0001). At month 12, 16 of 26 patients (62%) were PCR negative in peripheral blood. These results indicate that early molecular responses can be sustained for up to 12 months and that this response is highly correlated with progression-free survival. Rituximab has a high clinical activity and a low toxicity and induces a high complete molecular response rate in patients with follicular lymphoma and a low tumor burden.

Object: The authors present a retrospective analysis of 248 immunocompetent patients with primary intracerebral lymphoma treated at 19 French and Belgian medical centers between January 1980 and December 1995., Methods: This study involved 127 female and 121 male patients with a median age of 61 years (range 2-88 years). All tumors available for review were classic diffuse non-Hodgkin's lymphoma, for which the phenotype was determined in 220 patients: 212 (96.4%) were B-cell and eight (3.6%) were T-cell type tumors. According to the Revised European-American classification of lymphoid neoplasms, most lesions were diffuse large cell tumors (62%). A total of 196 tumors were reviewed in 127 patients for whom preoperative computerized tomography and magnetic resonance studies were available. There was a single lesion in 66% of the cases, with a supratentorial location in 87%. Tumor location in the basal ganglia, corpus callosum, or fornix, infiltration of the periventricular ependyma, or a mirror pattern, were strongly suggestive of a lesion of lymphomatous origin. The histological diagnosis was obtained after surgical resection in 116 patients, with the remainder undergoing biopsy sampling only. Of the 248 patients studied, 129 (52%) received chemotherapy plus radiation therapy, 60 (24%) received radiation therapy alone, 35 (14%) received chemotherapy alone, and 24 (10%) received no postsurgical treatment., Conclusions: Using univariate analysis, the authors determined prognostic factors that were significantly associated with a favorable impact on survival including age younger than 60 years, radiation therapy (without evidence of a dose-response relationship), radiation therapy combined with chemotherapy, and chemotherapy consisting of anthracycline. Partial surgical resection was an unfavorable prognostic factor. Multivariate analysis was used to confirm the independent prognostic value of radiation therapy, age, chemotherapy consisting of anthracyclines or methotrexate, and partial surgical resection. This European survey provides a reasonable basis for the treatment of primary intracerebral lymphoma with the following sequence: stereotactic biopsy sampling, chemotherapy with a methotrexate- and anthracycline-based regimen, followed by cranial irradiation.

Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome have recently been observed in patients undergoing interferon alpha (IFN-alpha) therapy. However, the relationship between disease and therapy has not been established, essentially because of concomitant treatment or previous bone marrow transplantation. We present a case of TTP developing during IFN-alpha therapy for chronic myelogenous leukemia. In this case, IFN-alpha seems to be the only etiological agent., (Copyright 2000 S. Karger AG, Basel)

Effective treatment in primary central nervous system lymphoma remains elusive. Usually high dose methotrexate and/or cytosine arabinoside may improve survival. We report the results of multimodality therapy in 248 patients (SFNC series). The addition of chemotherapy to radiation therapy and high dose methotrexate increased the duration of survival. We demonstrate that the use of anthracyclines in addition to radiation therapy had a significantly favorable impact on survival which is not reported in the literature. Survival was not longer in patients receiving intrathecal chemotherapy. The efficacy of chemotherapy alone has not been clearly defined.

Background: The International Prognostic Index (IPI) is widely used to predict outcome of patients with aggressive lymphomas. Our goal was to assess the prognostic value of this index for low-grade lymphoma., Patients and Methods: One hundred eighty-two patients with disseminated (stage III or IV) low-grade lymphoma were enrolled in a prospective multicenter trial. According to the initial features, treatment either was started immediately or was deferred until indicated by disease progression. Patients received the same polychemotherapy regimen, given monthly for six cycles. They were assigned to one of four risk groups according to the number of presenting risk factors: low-risk (0 or 1), low-intermediate-risk (2), high-intermediate-risk (3), high-risk groups (4)., Results: Survival curves (Kaplan-Meier method) demonstrated a high significant difference for the four groups (log-rank: P < 0.0001). Median survival for the low-risk group has yet to be reached, while that for the three other groups are, respectively, 65, 34, and 12 months., Conclusions: In this study, the IPI has been found to be an important prognostic tool in low-grade lymphoma and may be used in the selection of appropriate therapeutic approaches for individual patients.

We report a case of leukemic malignant T-cell lymphoma with mixed small and large cells. The small cells displayed a mature CD8-positive phenotype, a diploid DNA distribution by cell cycle analysis, and structural karyotypic abnormalities. Large cells were near triploid, showed additional structural cytogenetic abnormalities and a more immature membrane phenotype without CD8 expression. Altogether, these data provide suggestive evidence for a clonal evolution from a mature small cell T-cell lymphoma to a more immature large cell proliferation.

The capacity of alpha-interferon (alpha-IFN) to induce lymphokine activated killer (LAK) cytotoxicity in the absence of interleukin-2 (IL2) has prompted us to test whether its ability to reduce dramatically the number of Ph1+ clones in chronic myelogenous leukemia (CML) patients is in part mediated through the generation of natural killer (NK) or LAK activity. The latter were tested using NK-sensitive (K562) and NK-resistant (Raji) cell lines in a target-cell colony-growth inhibition assay. Effector cells (E) were patient blood mononuclear cells (MC) without in vitro activation prior to their coculture with targets (T). Here we report that cytogenetic remission in alpha-IFN-treated patients is associated with significantly enhanced NK and LAK activities. Nevertheless, some patients under alpha-IFN therapy were found to develop lymphoid blast crisis despite high levels of NK and LAK activities, and partial or total cytogenetic remission. In contrast, most of the patients who developed nonlymphoid blast crisis presented 100% Ph1+ cells and displayed defective NK and/or LAK activity. These observations could favor the hypothesis that there is an indirect but complex effect of alpha-IFN on leukemic cells, mediated by cells involved in immune surveillance; and also that lymphoid blast cells may actually escape LAK cytotoxicity.

The capacity of alpha-interferon (alpha-IFN) to induce lymphokine activated killer (LAK) cytotoxicity in the absence of interleukin-2 (IL2) has prompted us to test whether or not its ability to reduce dramatically the number of Ph1+ clones in chronic myelogenous leukaemia (CML) patients is in part mediated through the generation of natural killer (NK) or LAK activity. The latter were tested using NK-sensitive (K562) and NK-resistant (Raji) cell lines in a target-cell colony-growth inhibition assay. Effector cells (E) were patient blood mononuclear cells (MC) without in vitro activation prior to their coculture with targets (T). Out of 16 patients tested so far, three failed to undergo cytogenetic remission under alpha-IFN therapy. No NK nor LAK cells could be detected in the MC from two of them while the other displayed NK activity within upper normal limits. 13 patients underwent complete (eight) or partial (five) cytogenetic remission together with significantly high NK and/or LAK activity as compared to normal controls. These observations could favour the hypothesis of an indirect effect of alpha-IFN on leukaemic cells, mediated by cells involved in immune surveillance.

Interferons (INF) are glycoproteins with protean antiviral, immunomodulator, and antiproliferative actions. In Haematology, IFN-alpha is the most widely used. Diffusion into the spleen, bone marrow and liver is good. Hairy cell leukemia is probably the malignant blood disorder which responds best to IFN. At some time during their treatment, nearly 90% of the patients require IFN. Treatment initiation is indicated when pancytopenia (polynuclear neutrophils below 1 x 10(9)/L) develops or in case of a very voluminous spleen. IFN-alpha 2a, 2b and 2c are active (leukocyte IFN is used less often, as is IFN-beta; IFN-gamma is ineffective). The standard dose is 3 x 10(6) U, three times a week for 12 weeks. Smaller doses and maintenance treatment is sometimes proposed. Haematological remission occurs in almost all cases, if not a misdiagnosis must be considered (villous lymphocyte lymphoma). Relapse usually occurs at the end of treatment, but sensitivity to IFN is not altered and final survival is improved. Nearly 90% of the patients are alive at 4 years. Although IFN is active in chronic myeloid leukemia, research in this area continues. Clinical trials have reported haematologic relapse in 90% and complete cytogenetic response in 15 to 35% of the patients. The effect on Ph+ cells is not observed with classical chemotherapies. Initial dose is generally 5 x 10(6) U/m2/day. High doses are not always well tolerated, but cytogenetic response is only seen in patients in haematologic and cytopenic remission. IFN therapy improves survival over classical treatments (median 62 versus 39 months). Survival is better after good cytogenetic response or complete remission. Combined chemo-IFN therapy is currently under study in an attempt to improve cytogenetic response. In terms of the molecular biology however, residual disease is almost always present and relapse is frequent.(ABSTRACT TRUNCATED AT 250 WORDS)

Seraspenide, a synthetic tetrapeptide, inhibits cell cycle entry of normal hematopoietic stem cells. In mice it protects hemopoiesis against the damage caused by cytarabine, cyclophosphamide and carboplatin. Seraspenide has been given to 53 cancer patients undergoing monochemotherapy with cytarabine and ifosfamide in a double-blind cross-over randomized study. A significant protection of peripheral blood cells has been observed. Seraspenide has been devoided of toxicity.