Conjunctival low-grade non-Hodgkin's lymphoma: a large single-center study of initial characteristics, natural history and prognostic factors

To define the initial characteristics and prognostic factors of patients with conjunctival low-grade malignant lymphoma, all patients treated for low-grade lymphoma with initial conjunctival involvement were reviewed. Forty-nine cases were selected, including 45 cases with exclusive ophthalmologic conjunctival involvement. Pathologic review showed 55% of mucosa-associated lymphoid tissue type lymphoma, and 23% of lymphoplasmocytic lymphoma. Initial characteristics were median age of 62 years, nodal involvement in 17% of cases, and stage IV in 22% of patients with 10% of bone marrow involvement. With a median follow-up of 75 months, the 5-year disease-free survival (DFS) and overall survival were 65% and 83%, respectively. On multivariate analysis, nodal involvement was the only factor with a pejorative impact on DFS. Our patient cohort represents one of the largest published series defining the characteristics and prognostic factors of primary conjunctival low-grade malignant lymphoma.     

A prospective study of intensive induction therapy with high-dose consolidation in patients with aggressive non-Hodgkin's lymphoma and two or three adverse prognostic factors.

Patients with NHL and two or three factors of the International Prognostic Index (IPI) have a poor prognosis. We performed a prospective trial of intensive induction therapy followed with high-dose consolidation in such patients to determine the feasibility of this approach, as well as the response rate and survival. Untreated patients with aggressive lymphoma under the age of 60 with two or three adverse prognostic factors (disseminated stage, increased serum LDH, ECOG performance status >1) were prospectively included between June 1995 and April 1998 in a trial evaluating intensive induction chemotherapy with the ACE regimen (adriamycin day 1; cyclophosphamide days 1-2; etoposide days 1-3), with G-CSF support. Patients in complete remission after induction received one course of intensification with stem cell support (BEAM regimen), whereas patients in partial response received two intensifications (BEAM, then ICE regimens). Thirty-three patients (median age 38 years) were included. All patients presented WHO grade 4 leukopenia and 84% grade 3-4 thrombocytopenia during induction. There was one toxic death during induction. Twenty-nine patients proceeded to high-dose consolidation, including 12 patients who received a second high-dose treatment. The overall response rate was 88% (95% CI 76-99%), both after induction therapy and treatment completion. Thirty-nine percent of the patients had achieved complete remission after induction, and 73% after treatment completion. With a median follow-up after treatment onset of 29 months, the projected 3-year overall survival was 71% (95% CI 64-78%) and the event-free survival 58% (95% CI 50-66%). Event-free survival was significantly shorter in patients who did not achieve CR after induction therapy or after treatment completion. Early therapeutic intensification after intensive induction chemotherapy is feasible in patients with poor prognosis aggressive NHL and shows promising response and survival rates.     

Multivariate analysis of prognostic factors in stage IV follicular low-grade lymphoma: a risk model.

We analyzed the records of 96 previously untreated patients with stage IV follicular low-grade lymphoma (FLGL) uniformly treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo) chemotherapy from 1972 to 1982. The overall complete remission (CR) rate was 77%. At a median follow-up of 138 months, the 10-year cause-specific survival rate was 42% with a median survival of 100 months. Failure-free survival (FFS) was 15% at 10 years with a median FFS of 30 months. Multivariate analysis showed peripheral lymph node size (LN), degree of marrow involvement, and sex, in that order, to be important for FFS, while the number of extranodal sites (#ENS), LN, sex, and degree of marrow involvement were important for cause-specific survival. We devised a tumor burden (TB) model, incorporating #ENS, LN, and degree of marrow involvement. Three groups were identified with statistically significant differences in cause-specific survival and FFS. Those with low TB (one ENS exclusive of extensive marrow and nodal disease less than 5 cm) had a 10-year cause-specific survival of 73% compared with 24% for patients with high TB (greater than or equal to two ENS and nodal disease greater than or equal to 5 cm) (P less than .001) and 40% for those with intermediate TB (either greater than or equal to 2 ENS, or extensive marrow only, or nodal disease greater than 5 cm) (P = .050). Patients with low TB had a 10-year FFS rate of 32%, while the intermediate and high TB groups had 10% and 9% FFS, respectively (P = .003). Because sex was a very strong prognostic variable, we created a risk model for survival and FFS based on TB and sex. Females with low TB had the best prognosis (92% survival and 50% FFS at 10 years) and males with high TB had the worst outlook (median survival and FFS, 43 and 12 months, respectively). Other TB-sex combinations defined two groups with statistically significant differences in survival but comparable FFS. This model should aid in the design and analysis of future trials.     

Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M

One hundred sixty-three patients with advanced non-Hodgkin's lymphoma including adult T cell leukemia/lymphoma (ATL) were treated from 1981 to 1983 with VEPA (vincristine, cyclophosphamide, prednisolone, and doxorubicin) or VEPA-M (VEPA plus methotrexate) in randomized fashion after stratification by surface marker. The complete response (CR) rate and the 4-year survival rate of patients treated with VEPA-M was 62.2% and 36.9%, respectively, while for those treated with VEPA the rates were 51.9% and 26.6, respectively. The difference was not statistically significant, but pretreatment characteristics predictive for response and survival were interesting. Three factors, leukemic change, poor performance status (PS), and T cell marker, were negatively associated with both CR and survival rates, and high-grade pathology was adversely associated with survival rate in a multivariate analysis. These prognostic factors are somewhat different from those in Western lymphomas. This may be reflection of major differences in patients' characteristics between Japanese and Western lymphomas: in this study, there was a high incidence of T cell lymphoma/leukemia (50%) including ATL (33%), leukemic manifestation (34%), poor PS (34%), and a low incidence of follicular lymphoma (9%). The statistically significant three factors for both CR and survival rates were used to construct a model containing eight categories of patients at increasing risk for poor response and shortened survival. These categories were divided into four groups, with respective CR and 4-year survival rates of 91% and 73%, 67% and 35%, 27% and 7%, and 10% and 5%. Ninety-three patients in whom CR was induced by VEPA or VEPA-M therapy were evaluated for prognostic factors predictive for disease-free survival. A shorter period (less than 28 days) required to achieve CR, a clinical diagnosis of ATL, and a lower hemoglobin level were found to affect disease-free survival adversely. These results have important implications for both the design of prospective randomized therapeutic trials and the determination of optimal therapy for individual patients.     

A randomized trial of high dose cyclophosphamide, vincristine, and prednisone plus or minus doxorubicin (CVP versus CAVP) with long-term follow-up in advanced non-Hodgkin's lymphoma

Ninety-three stage III and IV patients with non-Hodgkin's lymphoma were randomized to either high dose CVP (cyclophosphamide 1500 mg/m2 i.v. day 1, vincristine 1.4 mg/m2 day 1, and prednisone 40 mg/m2 orally days 1-10) or high dose CAVP (cyclophosphamide 1000 mg/m2 i.v. day 1, doxorubicin 45 mg/m2 i.v. day 1, vincristine and prednisone as above). Overall, the complete response (CR) rates were similar (CVP 51%, CAVP 51%). Patients with the International Working Formulation diffuse large cell lymphoma had significantly higher CR with CAVP. No difference in CR duration was detected between the two regimens. CRs were durable with 68% of diffuse and 86% of diffuse large cell complete responders alive and disease free at 7 years. Survival was similar with both regimens except for patients with diffuse large cell lymphoma who survived longer with CAVP. Both regimens were equitoxic with neutropenia less than 1.0 x 10(9)/liter in 36% of courses, infections in 15% of courses, and fatal infections in three patients. These intermittent high dose cyclophosphamide equitoxic regimens produced durable responses. However, the doxorubicin-containing regimen is superior in diffuse large cell lymphoma.     

Long-term results in patients with low-grade nodular non-Hodgkin's lymphoma. A randomized trial comparing chemotherapy plus radiotherapy with chemotherapy alone

One hundred and eighteen patients with nodular non-Hodgkin's lymphoma were randomized to receive either chemotherapy alone or chemotherapy plus radiotherapy (total nodal or involved field irradiation). Although the complete remission rate was similar in the three programs (about 90%) the relapse-free survival rate (RFS) among patients with complete remission was significantly higher in the groups treated with chemotherapy plus radiotherapy than among those treated with chemotherapy alone. The 7-year RFS in the groups treated with total node irradiation and involved field irradiation was 71% and 66% respectively, compared to only 33% in the group treated by chemotherapy alone (p less than 0.01). The results suggest that combined chemoradiotherapy may achieve complete long-term remission and potential cure in more than 60% of patients with nodular low-grade non-Hodgkin's lymphoma. Toxicity was moderate in all three arms. Bulky disease and a high level of lactic dehydrogenase were associated with a poor prognosis.     

Chemotherapy followed by consolidation radiation therapy for the treatment of clinical stage II aggressive histologic type non-Hodgkin's lymphoma

Sixty-three eligible patients with Ann Arbor clinical Stage II or IIE aggressive histologic type non-Hodgkin's lymphomas received combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [COPA]) as the primary treatment technique. Moderate-dose radiation therapy (2500 to 3000 cGy in 2 to 3 weeks) was given to anatomic areas involved initially by lymphoma in patients demonstrated to be in complete remission after chemotherapy. Fifty-seven percent of the patients were free of lymphoma clinically after induction chemotherapy. The minimum patient follow-up from the start of chemotherapy is 3.7 years, and the median follow-up for patients still alive is 4.7 years. The progression-free survival is projected to be 62% at 4 years, and 86% of the patients achieving a complete response are projected to be in continuous remission at 4 years from the completion of all therapy. There were no treatment-related fatalities. This treatment sequence has produced durable tumor control in the majority of patients with acceptable toxicity. The need for consolidation radiation therapy is being studied currently in a controlled clinical trial.     

Long-term follow-up of a prospective study of combined modality therapy for stage I-II indolent non-Hodgkin's lymphoma.

PURPOSE: Standard therapy for patients with stage I-II indolent lymphoma has been involved-field radiation therapy (IF-XRT), which achieves 10-year disease-free survival in 40% to 50% of patients, with many of these patients cured. We investigated the potential for combined-modality therapy to increase the disease-free survival for such patients. PATIENTS AND METHODS: A total of 102 eligible patients with stage I-II low grade lymphoma (International Working Formulation criteria) were enrolled from 1984 to 1992. Treatment comprised 10 cycles of risk-adapted chemotherapy (cyclophosphamide, vincristine, prednisone, bleomycin [COP-Bleo], and with doxorubicin added for some [CHOP-Bleo]) and 30 to 40 Gy IF-XRT. RESULTS: The patients' median age was 56 years (range, 28 to 77), with follicular histology in 83%, bulky disease (>/= 5 cm) in 24%, and stage II in 52%. There were no treatment-related deaths and 99% of patients attained complete remission. With a median follow-up of 10 years, the 10-year time to treatment failure and overall survival were 76% and 82%, respectively. For patients with follicular lymphoma, these figures were 72% and 80%, respectively. The only factor associated with treatment failure, for follicular lymphoma patients, was stage-modified International Prognostic Factors Index score (P =.02). None of 17 patients with diffuse small lymphocytic or mucosa-associated lymphoid tissue histology have relapsed. Elevated serum beta2-microglobulin was associated with shorter survival (P <.0001). The 10-year survival after relapse was 46%. There have been two cases of myelodysplasia and 12 other new malignancies, including four arising within radiation fields. CONCLUSION: With prolonged follow-up, combined-modality therapy with risk-adapted COP-/CHOP-Bleo and IF radiation has attained higher rates of disease control and survival than previously reported with IF-XRT alone. This apparent improvement is being further explored in an ongoing randomized trial.     

Phase II study of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C alpha, in patients with previously treated low-grade non-Hodgkin's lymphoma.

BACKGROUND: The purpose of this study was to assess the efficacy and safety of ISIS 3521, an antisense phosphorothioate oligonucleotide to protein kinase C alpha in patients with relapsed low-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Twenty-six patients received ISIS 3521 (2 mg/kg/day) as a continuous infusion over 21 days of each 28-day cycle. RESULTS: The median age of the patients was 53 years (range 37-77). Histological subtypes were low-grade follicular lymphoma (n = 22) and B-cell small lymphocytic lymphoma (n = 4). Twenty-one (81%) had stage III/IV disease. The median number of previous lines of chemotherapy was two (range one to six). A total of 87 cycles of ISIS 3521 were administered. Twenty-three patients were assessable for response. Three patients achieved a partial response. No complete responses were observed. Ten patients had stable disease. Grade 3-4 toxicity was as follows: neutropenia (3.8%) and thrombocytopenia (26.9%). CONCLUSIONS: ISIS 3521 has demonstrated anti-tumour activity in patients with relapsed low-grade NHL. There may be a potential role for this agent in combination with conventional chemotherapy for advanced low-grade lymphoma, and further trials are warranted.     

Activity of fludarabine in previously treated non-Hodgkin's low-grade lymphoma: results of an Eastern Cooperative Oncology Group study.

PURPOSE: Fludarabine (2-fluoro-arabanoside-monophosphate) is a new antimetabolite chemotherapeutic agent. We performed a multicenter, phase II study of this drug in previously treated patients with refractory or relapsed non-Hodgkin's lymphoma (NHL) to determine its response rate by histologic classification. PATIENTS AND METHODS: Sixty-two assessable patients were given 18 mg/m2 by intravenous (IV) bolus injection daily for 5 days, every 28 days. Forty-eight percent had previously had one chemotherapy regimen, and the remainder had had two regimens; 42% had had radiation. RESULTS: Patients received 273 cycles of fludarabine chemotherapy, with a median of two cycles and ranging up to 25 cycles. Sixty patients were assessable for response, including nine complete responses (CRs; 15%) and nine partial responses (PRs; 15%). The response rate for patients with lower-grade histology was 52% (13 of 25); the greatest response rate was seen in those with follicular small cleaved-cell lymphoma, including seven of 11 treated. Five responders remain in unmaintained remission; the median survival of responders is greater than 30 months. Toxicity included mild neutropenia and a 10% incidence of grade 3 neurologic toxicity with occasional reversible visual and auditory changes. CONCLUSION: Fludarabine is active in patients with previously treated NHL (particularly low-grade histologies). Future studies will examine its activity in combination with other chemotherapeutic agents in previously untreated patients.     

Results of a randomized phase III trial in children and adolescents with advanced stage diffuse large cell non-Hodgkin's lymphoma: a Pediatric Oncology Group study

PURPOSE: The Pediatric Oncology Group (POG) adopted a histology-based approach to the management of pediatric non-Hodgkin's lymphomas (NHL) utilizing the National Cancer Institute Working Formulation for Clinical Usage. Patients with diffuse large cell lymphoma (DLCL) were treated on a separate protocol from small cell diffuse undifferentiated or lymphoblastic lymphomas. This study assessed the overall and event free survival of children with DLCL and determined the effects of cyclophosphamide upon these end-points in a prospective randomized trial. PATIENTS AND METHODS: One hundred and twenty eligible stage III or IV NHL patients with the confirmed diagnosis of diffuse large cell or immunoblastic histology were enrolled on study between October 1986 and November 1991. Patients were randomized to receive or not receive cyclophosphamide: 58 received cyclophosphamide, doxorubicin, vincristine, 6-mercaptopurine (6-MP), and prednisone (ACOP+) and 62 were treated with doxorubicin, vincristine, 6-MP, and prednisone (APO). In both treatment programs methotrexate was substituted when the doxorubicin cumulative dose reached 450 mg/m2. Radiation was administered to bulky disease if progression or no response were observed after induction therapy. Planned duration of therapy was 12 months. RESULTS: The 5-year event free survival (EFS) rates of patients treated with ACOP+ versus APO were 62+/-7 and 72+/-6%, respectively. While there was no statistically significant difference between the two treatment arms (p = 0.28), we can only say that we are 95% confident that the difference in 5-year EFS falls in the wide range from 28% in favor of APO to 8% favoring ACOP+. Marrow suppression was the main toxicity with one fatal infection. There were three other deaths on study due to respiratory failure in patients with mediastinal masses. Only one patient experienced cardiotoxicity requiring discontinuation of doxorubicin. Ten patients received radiation therapy to achieve remission. CONCLUSION: The efficacy of elimination of cyclophosphamide from the treatment program of children and adolescents with advanced stage diffuse large cell lymphoma was inconclusive as to its effect on EFS. Furthermore, the majority of the patients (92%) did not require any radiation therapy to bulky disease indicating that the chemotherapy regimens are quite efficient for achievement of complete remission.     

Open-label, randomized study of pegfilgrastim vs. daily filgrastim as an adjunct to chemotherapy in elderly patients with non-Hodgkin's lymphoma

Pegfilgrastim is composed of the protein filgrastim to which a 20-kDa polyethylene glycol (PEG) is covalently bound at the N-terminal residue resulting in decreased renal clearance and increased plasma half-life compared with filgrastim. This open-label, randomized, phase 2 study compared two doses of single administration pegfilgrastim (60 and 100 microg/kg) with daily doses of filgrastim (5 microg/kg/day) or no cytokine treatment after standard CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy for non-Hodgkin's lymphoma in 50 elderly patients. The primary endpoint was the duration of grade 4 (severe) neutropenia (absolute neutrophil count < 0.5 x 10(9)/l) in cycle 1. Duration of grade 4 neutropenia in cycle 1 was 2.2 (SD 1.2), 1.5 (SD 1.1), 0.8 (1.2) and 5.0 (2.0) days for patients who received pegfilgrastim 60 microg/kg, pegfilgrastim 100 microg/kg, filgrastim 5 microg/kg and no cytokine, respectively. The baseline characteristics of the pegfilgrastim and filgrastim groups were imbalanced with increased bone-marrow involvement and prior therapy in the former. When the treatment groups were balanced for these risk factors, duration of grade 4 neutropenia was comparable with 2.0 and 3.0 vs. 0.6 and 0.5 days for pegfilgrastim 100 microg/kg and filgrastim patients with and without these risk factors, respectively. The incidence of febrile neutropenia (defined as ANC < 0.5 x 10(9)/l and temperature > 38.2degrees C) was low (10% of patients). Pegfilgrastim was well tolerated with a safety profile similar to daily filgrastim. Once per chemotherapy cycle administration of pegfilgrastim was comparable to filgrastim in this clinical setting.     

Interferon alpha consolidation after intensive chemotherapy does not prolong the progression-free survival of patients with low-grade non-Hodgkin's lymphoma: results of the Southwest Oncology Group randomized phase III study 8809.

PURPOSE: S8809 is a randomized phase III trial determining whether intensive cytoreductive treatment, followed by interferon consolidation at the time of minimal residual disease, prolongs the progression-free survival (PFS) or overall survival (OS) of indolent lymphoma patients. PATIENTS AND METHODS: Five hundred seventy-one patients with previously untreated stage III or IV low-grade non-Hodgkin's lymphoma were registered. Patients received six to eight cycles of prednisone, methotrexate, doxorubicin, cyclophosphamide, and etoposide/mechlorethamine, vincristine, procarbazine, and prednisone (ProMACE[day 1]-MOPP[day 8]) chemotherapy or chemotherapy plus radiotherapy. Responding patients were randomized to observation alone or to interferon consolidation. Interferon alpha-2b 2 mU/m(2) was given subcutaneously three times weekly for 2 years. RESULTS: Two hundred sixty-eight eligible patients were randomized to interferon alpha consolidation (n = 144) or observation alone (n = 124). With a median follow-up time from randomization among patients still alive of 6.2 years, the median PFS time was 4.1 years for patients who received interferon consolidation therapy and 3.2 years for patients who were observed after ProMACE-MOPP induction (P =.25). The adjusted hazard ratio for relapse for observation to interferon was 0.83 (95% confidence interval [CI], 0.61 to 1.13). The median OS has not been reached in either group. At 5 years, OS is 78% for the interferon group and 77% for the observation group (P =.65). The adjusted hazard ratio for survival for observation to interferon is 1.11 (95% CI, 0.69 to 1. 79). CONCLUSION: Interferon alpha consolidation therapy after intensive treatment with anthracycline-containing combination chemotherapy and involved-field radiation therapy does not prolong the PFS or OS of patients with low-grade non-Hodgkin's lymphoma.     

Prognostic factors in non-Hodgkin's lymphoma: the importance of symptomatic stage as an adjunct to the Kiel histopathological classification.

A prospective study of prognostic factors for patients with non-Hodgkin''s lymphoma was carried out based on the Kiel histopathological classification. Other presentation features assessed for prognostic value included clinical features, haematological and biochemical findings, and immunochemical findings. The most powerful factors that emerged were the presence or absence of systemic symptoms and the histopathological grade of malignancy of the lymphoma (whether low or high grade). These 2 factors were largely independent. Clinical Stage I disease also carried a good prognosis, but beyond this, staging gave little further prognostic information. Nine of the group of 15 patients with Stage I high grade lymphoma have achieved prolonged disease-free survival after local therapy only. After allowing for histopathology and symptom assessment in patients with Stage II-IV disease, other factors, with the exception of C-reactive protein levels, were of minor importance.     

A clinicopathologic study of node-based, low-grade, peripheral T-cell lymphoma. Angioimmunoblastic lymphoma, T-zone lymphoma, and lymphoepithelioid lymphoma.

Postthymic (peripheral) T-cell malignancy shows marked diversity in histopathologic appearances as well as in clinical and prognostic aspects. Histologic findings and clinical behavior of 110 cases of the three specific types of low-grade, peripheral T-cell lymphomas, i.e., lymphoepithelioid (LeL), angioimmunoblastic (AILD), and T-zone (TzL) lymphomas, were studied. There were 74 men and 36 women (age range, 24 to 90 years; median, 58). Histologic study of LeL, AILD, and TzL showed prominent reactive features which are distinct from those of high-grade, T-cell lymphomas (pleomorphic/immunoblastic types). Corresponding to the differences in the histologic pictures of each type, there were differences in the clinical pictures and prognosis. Hypergammablobulinemia (greater than 4 g/dl) was more common in AILD than in the others. However, these three types exhibited a widely variegated, sometimes overlapping spectrum of histologic appearances, and it was extremely difficult to distinguish one from the other on several occasions. The same was true of their clinical and laboratory findings, and they had a relatively favorable prognosis as compared with pleomorphic/immunoblastic lymphomas. Although the conventional phenotypic analysis showed the prominent mixture of helper/inducer and cytotoxic/suppressor T-cells with a varying degree of B-cells and histiocytes, the double immunohistochemical study revealed that the neoplastic cells consisted predominantly of helper/inducer cells. Furthermore, five cases (5%) showed the morphologic transition among the three types or development into pleomorphic/immunoblastic lymphoma. They seemed to constitute a comprehensive and yet distinct group of T-cell lymphomas. Based on morphologic findings and clinical data, the authors demonstrated the distinct character of the node-based, low-grade, T-cell lymphomas and also the relationship among the three types in this group. The results of phenotypic and genotypic analyses also support the concept proposed here.     

Peritoneal carcinomatosis in nongynecologic malignancy. A prospective study of prognostic factors

Regional recurrence of malignant tumors in the peritoneal cavity usually signifies a poor prognosis for the host and often results in gastrointestinal complications requiring surgical intervention. One hundred patients with nongynecological malignancies found with peritoneal carcinomatosis were followed prospectively. The most common primary tumors were colorectal (N = 45) and pancreatic (N = 20) carcinoma. When associated with pancreatic carcinoma, 65% of patients had liver metastases and 60% had ascites. The presence of ascites was associated with poor survival, with no patient surviving past 30 days. Ascites was also a sign of poor prognosis in patients with colorectal carcinoma. Among possible prognostic factors in colorectal carcinoma patients, only disease-free interval, presence of lung metastases, and ascites showed statistically significant correlations with survival. Peritoneal carcinomatosis in sarcoma (N = 7) and breast cancer (N = 6) patients had median survival of 12 and 7 months, respectively. Surgical intervention for gastrointestinal complications in peritoneal carcinomatosis can provide significant palliation, with a few exceptions such as in patients with pancreatic or gastric carcinoma, ascites, and poor performance status.     

Primary non-Hodgkin's high grade malignant lymphoma of the digestive system. A prospective study of the combination of surgery-chemotherapy-radiotherapy

We report a prospective study concerning the association of surgery-chemotherapy and radiotherapy in the treatment of primary high grade digestive non-Hodgkin's lymphomas in 19 patients. The analysis of 11 stages IE, 5 stages II1E and 3 stages II2E allowed us to evaluate the efficacy and the tolerance of this triple therapeutic association. Fifteen patients are alive and well with a median follow-up of 54 months. One of these patients relapsed, but after autologous bone marrow transplantation is in second unmaintained complete remission. Four patients died of intercurrent aetiology although one death was related to treatment morbidity. Our results and the analysis of literature data lead us to recommend the triple association in the treatment of stage II2E high grade primary digestive lymphomas (PDL) and for PDL without complete resection. However, surgery and chemotherapy appear to be sufficient in the treatment of stages IE and II1E with complete resection.     

Ophthalmologic and intraocular non-Hodgkin's lymphoma: a large single centre study of initial characteristics, natural history, and prognostic factors

The aims of this study were to define the initial characteristics, natural history, and prognostic factors of patients with ophthalmologic and intraocular malignant lymphoma. All patients treated at the Institut Curie for lymphoma with ophthalmologic (orbit and/or adnexa) or intraocular involvement were retrospectively reviewed. A pathological review of all cases was performed according to the WHO classification. One hundred and forty-five patients were selected for the study. Pathological review showed 36% MALT type lymphoma, 22% lymphoplasmocytic lymphoma, and 15% diffuse large B-cell lymphoma. Ophthalmologic and ocular sites were intra-orbital in 61 cases (42%) and conjunctival in 51 cases (35%), with bilateral involvement in 10% of cases. Stage IV was found in 32% of cases, with bone marrow involvement in 12%. With a median follow-up of 90 months, the 5-year DFS and OS were 64 and 79% for low-grade NHL, and 43 and 50% for high-grade NHL. On multivariate analysis, age greater than 59 years, elevated LDH level, stage IV, high-grade histological subgroup, and presence of B-symptoms had a negative impact on OS for the overall population. In conclusion, with a median follow-up of 7.5 years, our large cohort of patients represents one of the largest published series on primary ophthalmologic and intraocular malignant lymphoma.     

Long-term follow-up of a randomized trial of fludarabine-mitoxantrone, compared with cyclophosphamide, doxorubicin, vindesine, prednisone (CHVP), as first-line treatment of elderly patients with advanced, low-grade non-Hodgkin's lymphoma before the era of monoclonal antibodies.

BACKGROUND: This randomized study compared the efficacy and safety of fludarabine-mitoxantrone (FM) with mini-CHVP (cyclophosphamide, doxorubicin, vindesine, prednisone) in elderly patients with advanced, low-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: End points were remission rates [overall response (OR) and complete response (CR)], failure-free survival (FFS), survival and toxicity. One hundred and fifty-five patients were randomized, 144 were evaluable for safety and 142 for response. Each treatment arm was given as six monthly cycles, followed by three bimonthly cycles. FM comprised fludarabine (20 mg/m(2) i.v.), days 1-5, plus mitoxantrone (10 mg/m(2) i.v.), day 1. CHVP cycles comprised cyclophosphamide (750 mg/m(2) i.v. infusion), doxorubicin (25 mg/m(2) i.v.) and vindesine (3 mg/m(2) i.v.) on day 1, and prednisone (50 mg/m(2)) on days 1-5. RESULTS: FM therapy resulted in superior remission rates (OR 81% versus 64%, CR 49% versus 17%; P = 0.0004). Median FFS for FM patients was 36 months, compared with 19 months for CHVP patients, and has not yet been reached for early CR patients at 53 months. Treatment arm was the major risk factor influencing survival. Both treatments were well tolerated, with only few infectious complications. CONCLUSION: FM was more effective than CHVP in achieving OR and CR, and favorably affected the outcome.