levoleucovorin and Lymphoma--Large-B-Cell--Diffuse

Within diffuse large B-cell lymphomas, the Primary Mediastinal Large B-Cell Lymphoma has to be considered as a separate and well-defined clinico-pathological entity. Its tendency to target young adults makes its social impact particularly significant; hence, the General Practitioner carries the responsibility for an early diagnosis. On the contrary, the extreme complexity of the available therapies makes a quick referral to specialized Clinical Centres of outmost importance, since this remains the best way to enrol as many patients as possible in therapeutic protocols. Nowadays, good clinical results and a favourable outcome are achievable, but some questions remain open. The role of radiotherapy still has to be clarified, both as a complete remission consolidation, as well as a treatment of the residual disease. Conversely, a golden standard for the second line treatment has not been clearly established.

Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chemoradiotherapy; Chest Pain; Cyclophosphamide; Diagnostic Imaging; Doxorubicin; Dyspnea; Early Diagnosis; Humans; Immunophenotyping; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Mediastinal Neoplasms; Methotrexate; Multicenter Studies as Topic; Neoplasm Staging; Prednisone; Prognosis; Randomized Controlled Trials as Topic; Rituximab; Salvage Therapy; Symptom Assessment; Vincristine

Primary mediastinal large-B cell lymphomas (PMLCL) are considered to be a distinct clinicopathologic entity among the diffuse large B-cell lymphomas. This study evaluated the prognostic factors and therapeutic outcome of PMLCL in a single-institution series. Twenty seven patients were reviewed. Nineteen of the 27 had Stage I-II and 8 had Stage III-IV disease. B-symptoms were found in 11 (41%) and bulky disease in 10 (37%) patients. All were initially given combination chemotherapy (CT): doxorubicin-containing regimens to 23 patients (11 patients had CHOP, 12 received more intensive third-generation regimens) and 4 elderly (>70 years) patients received CVP. Eleven responders were consolidated with irradiation (RT) as part of their initial treatment, with a median total dose of 39 Gy. Nineteen patients (70%) achieved clinical remission (15 CR and 4 PR) with their initial therapy. Forty-four percent of patients remained progression-free and 59% are alive at 3 years. The actuarial 10-year time to progression (TTP) and overall survival (OS) were 44% and 50%, respectively. Age >60 years, performance status >1 and IPI intermediate-high to high risk were significantly associated with poorer OS and TTP by univariate analysis (log-rank test). A better outcome was associated with the use of more aggressive chemotherapy regimens or with the inclusion of RT in the first-line treatment. Our analyses suggest that the application of radiotherapy in combination regimens and the use of more aggressive chemotherapy in the treatment of this particular type of lymphoma should now be evaluated in prospective randomized trials.

Topics: Actuarial Analysis; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Controlled Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Disease-Free Survival; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Mediastinal Neoplasms; Methotrexate; Middle Aged; Prednisone; Procarbazine; Prognosis; Prospective Studies; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Remission Induction; Thymus Neoplasms; Treatment Outcome; Vincristine

Patients with malignant lymphoma, diffuse type, have an unfavorable prognosis when compared to those patients with modular patterns. Prior to the introduction of combination chemotherapy, 50% survival rates for MC-D or PDL-D were about 2 years, HL-D about 1 year. Aggressive combination chemotherapy for advanced MC-D or PDL-D results in complete remission rates of 22-82%, with median survivals of 1-2 years. Patients with localized HL-D are probably curable with radiotherapy alone in 75% of cases. Patients with advanced disease are best treated with intensive combination chemotherapy, achieving a long-lasting complete remission in over one-half of cases, with median survivals now at 1-3 years. Many of these patients are probably cured, central nervous system relapse may now be a concern. The results of treatment of advanced histiocytic lymphoma are now approaching the results reported for advanced Hodgkin disease.

Topics: Antineoplastic Agents; Central Nervous System Diseases; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Humans; Leucovorin; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Methotrexate; Neoplasms; Prednisone; Remission, Spontaneous; Vincristine

Topics: Adult; Aged; Antineoplastic Agents; Bone Marrow; Burkitt Lymphoma; Child; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Leucovorin; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prognosis; Remission, Spontaneous; Time Factors

Topics: Alkaloids; Alkylating Agents; Antibiotics, Antineoplastic; Antimetabolites; Antineoplastic Agents; Cell Survival; Child; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Humans; Immunotherapy; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Methotrexate; Neoplasms; Plants, Medicinal; Vincristine

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Female; Humans; Lenalidomide; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Rituximab; Survival Analysis

To assess the role of [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) after rituximab and anthracycline-containing chemoimmunotherapy in patients with primary mediastinal large B-cell lymphoma (PMLBCL).. Among 125 patients prospectively enrolled, 115 were eligible for central review of PET/CT scans at the completion of standard chemoimmunotherapy, by using a five-point scale. Consolidation radiotherapy (RT) was permitted and given to 102 patients.. Fifty-four patients (47%) achieved a complete metabolic response (CMR), defined as a completely negative scan or with residual [18F]FDG activity below the mediastinal blood pool (MBP) uptake. In the remaining 61 patients (53%), the residual uptake was higher than MBP uptake but below the liver uptake in 27 (23%), slightly higher than the liver uptake in 24 (21%), and markedly higher in 10 (9%). CMR after chemoimmunotherapy predicted higher 5-year progression-free survival (PFS; 98% v 82%; P=.0044) and overall survival (OS; 100% v 91%; P=.0298). Patients with residual uptake higher than MBP uptake but below liver uptake had equally good outcomes without any recurrence. Using the liver uptake as cutoff for PET positivity (boundary of score, 3 to 4) discriminated most effectively between high or low risk of failure, with 5-year PFS of 99% versus 68% (P<.001) and 5-year OS of 100% versus 83% (P<.001).. More than 90% of patients are projected to be alive and progression-free at 5 years, despite a low CMR rate (47%) after chemoimmunotherapy. This study provides a basis for using PET/CT to define the role of RT in PMLBCL.

Topics: Adult; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Fluorodeoxyglucose F18; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Mediastinal Neoplasms; Methotrexate; Multimodal Imaging; Positron-Emission Tomography; Predictive Value of Tests; Prednisone; Prognosis; Radiopharmaceuticals; Rituximab; Survival Analysis; Tomography, X-Ray Computed; Vincristine

The optimal treatment of primary mediastinal large B-cell lymphoma (PMLBCL) is still undefined. In the absence of randomised studies, we retrospectively analysed: (a) the effectiveness of two chemotherapy regimens (CHOP vs MACOP-B/VACOP-B) in complete remission (CR) achievement and event-free survival (EFS) and (b) the role of mediastinal involved-field radiotherapy (IF-RT) as consolidation. From 1982 to 1999, 138 consecutive patients affected by PMLBCL were treated in 13 Italian institutions with CHOP (43) or MACOP-B/VACOP-B (95). The two groups of patients were similar as regard to age, gender, presence of bulky mediastinal mass, pleural effusion, stage and international prognostic indexes category of risk. Overall, 75.5% of patients in CR received IF-RT as consolidation. Complete remission was 51.1% in the CHOP group and 80% in MACOP-B/VACOP-B (P<0.001). Relapse occurred in 22.7% of CHOP- and in 9.2% of MACOP-B/VACOP-B-treated patients (n.s.). Event-free patients were 39.5% in CHOP and 75.7% in the MACOP-B/VACOP-B group (P<0.001). The addition of IF-RT as consolidation improved the outcome, irrespectively of the type of chemotherapy (P=0.04). At a multivariate analysis, achievement of CR (P<0.0001) and type of CT (MACOP-B/VACOP-B) retained the significance for OS (P=0.008) and EFS (P=0.03). In our experience, MACOP-B/VACOP-B appears to positively influence OS and EFS in patients affected by PMLBCL, as compared to CHOP. Consolidation IF-RT on mediastinum further improves the outcome of CR patients.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Etoposide; Female; Humans; Leucovorin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Mediastinal Neoplasms; Methotrexate; Middle Aged; Prednisone; Prognosis; Retrospective Studies; Risk Factors; Treatment Outcome; Vincristine

The purpose of this study was to investigate the prognostic effects of four biological markers, BCL2, TP53, Ki-67, and P-glycoprotein, and their possible clinical relevance in addition to the international prognostic index (IPI) in diffuse large B-cell lymphoma (DLBCL). A total of 405 patients with aggressive lymphoma, stage II-IV, between 18 and 67 years, were randomized in a trial comparing CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin). Of these, 267 cases were classified as DLBCL, with adequate paraffin blocks available in 207 cases, enabling immunohistochemical assessment of the expression of BCL2, TP53, P-glycoprotein, and Ki-67. In a multivariate analysis, stratified for IPI, high BCL2 expression (>10%) low (<60%) expression of Ki-67, and high TP53 protein expression (>75%) were shown to provide additional prognostic information with regard to overall or failure-free survival. We found no association between expression of P-glycoprotein and outcome. Assessment of BCL2 positivity might be introduced as part of the routine investigation in patients with DLBCL, but further studies are necessary to confirm the clinical relevance of Ki-67 and TP53 expression.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biomarkers; Bleomycin; Cohort Studies; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Female; Humans; Ki-67 Antigen; Leucovorin; Life Tables; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Neoplasm Proteins; Neoplastic Stem Cells; Norway; Prednisone; Prognosis; Proto-Oncogene Proteins c-bcl-2; Risk Factors; Survival Analysis; Sweden; Treatment Outcome; Tumor Suppressor Protein p53; Vincristine

The purpose of this study was to investigate the prognostic implications of BCL6 rearrangement in a uniformly treated population of patients with diffuse large B-cell lymphoma (DLBCL) and to characterise the relationship between BCL6 rearrangement and prognostic factors. A total of 269 patients with DLBCL entered a randomised trial comparing the chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) to the MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) regimen. In 44 cases, frozen tissue was available for assessment of BCL6 status by Southern blot analysis. BCL6 was rearranged in six of 43 evaluable cases (14%), and was associated with elevated lactate dehydrogenase (LDH), and a higher patient age. No association between BCL6 status and expression of BCL2, Ki-67 or TP53 was found. Patients presenting with BCL6 rearrangement displayed a weak trend towards better overall and failure-free survival (67 and 67% at 5 years), compared to patients with germline BCL6 (63 and 52%), but the difference was not statistically significant. In accordance with previously published series, the presence of BCL6 rearrangement does not define a prognostically distinct subgroup of DLBCL. Assessment of BCL6 status may, however, be of clinical interest when related to other prognostic variables.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Blotting, Southern; Cyclophosphamide; DNA-Binding Proteins; DNA, Neoplasm; Doxorubicin; Gene Rearrangement, B-Lymphocyte; Humans; Immunophenotyping; L-Lactate Dehydrogenase; Leucovorin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Neoplasm Staging; Prednisone; Prognosis; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-6; Transcription Factors; Vincristine

Mitoxantrone, etoposide and prednisone (MEP)-based regimens using granulocyte colony-stimulating factor (G-CSF) were designed for relapsed and CHOP-resistant diffuse large B-cell lymphomas in a single institution, and the therapeutic effects and adverse reactions were studied. In a total of 49 patients, the MEP regimen had a 41% (9/22) overall response rate compared with 48% (13/27) for the MEP plus carboplatin (C-MEP) regimen (Chi-squared test, P=0.602). Among 38 CHOP-resistant patients, however, the overall response rate to C-MEP [42% (10/24)] was significantly superior compared with MEP [7% (1/14)] (P=0.023), and the overall survival to C-MEP was superior compared with MEP (P=0.088). Taken together, our results, although non-randomized, suggest that a combination of MEP with carboplatin is better than MEP alone in CHOP-resistant diffuse large B-cell lymphomas.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Drug Resistance, Multiple; Etoposide; Female; Follow-Up Studies; Humans; Leucovorin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Mitoxantrone; Neoplasm Staging; Prednisone; Recurrence; Survival Rate; Time Factors; Vincristine

Patients with primary central-nervous-system lymphoma (PCNSL) are treated with chemotherapy and cranial irradiation, which increase the risk of late neurotoxicity. The aim of this phase II trial was to investigate whether chemotherapy alone could induce durable remissions. Thirty non-immunocompromised patients were enrolled in two treatment groups, according to age. Patients in group A (< 65 years; n = 17) received carmustine, vincristine, dexamethasone, high-dose methotrexate and high-dose cytarabine. Patients in group B > 65 years: n = 13) were treated with carmustine, vincristine, dexamethasone and high-dose cytarabine. Both groups received intrathecal treatment. Radiotherapy was reserved for patients with stable or progressive disease. The overall response rate in group A was 65% (complete response 35%; partial response 29%) and in group B. 61% (complete response 23%; partial response 38%), but only 6 remissions were maintained without irradiation. In all, there were five treatment-related deaths. Responses were induced, but were mostly of short duration, and the treatment was associated with profound toxicity.

Topics: Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Central Nervous System Neoplasms; Cytarabine; Dexamethasone; Female; Follow-Up Studies; Humans; Injections, Spinal; Leucovorin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, T-Cell; Male; Middle Aged; Pilot Projects; Radiotherapy, Adjuvant; Vincristine

Primary mediastinal large B-cell lymphoma (PMLBCL) with sclerosis has recently been recognized as a specific clinical and pathologic entity for which the best therapeutic approach seems to be a combination of chemotherapy and radiotherapy.. Between 1989 and 1998, 89 previously untreated patients with PMLBCL with sclerosis were treated with a combination of a third-generation chemotherapy regimen (MACOP-B) and mediastinal radiation therapy. The response evaluations were examined after chemotherapy and at the end of radiotherapy.. Twenty-three (26%) patients achieved a complete response (CR) and 59 (66%) obtained a partial response (PR) after the MACOP-B regimen. After radiation therapy, 55/59 (93%) of the patients in PR achieved CR. The CR rate at the end of the treatment was 88% (78/89). Only 7 (8%) patients were non-responders. Among the 78 patients who obtained a CR there were 7 (9%) relapses in a median follow-up of 5 months (all relapses occurred within 9 months); the other 71 patients are currently in continuous CR with a median follow-upof 45 months (range, 4-110 months). Projected overall survival was 86% at 9 years; the relapse-free survival curve of the 78 patients who achieved CR was 91% at 9 years.. In patients with PMLBCL with sclerosis, combined modality treatment using the MACOP-B chemotherapy regimen and radiation therapy induces a good remission rate with the patients having a greater than 90% chance of surviving disease-free at 9 years. Radiotherapy often plays a pivotal role in obtaining CR status.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Mediastinal Neoplasms; Methotrexate; Middle Aged; Prednisone; Sclerosis; Survival Rate; Treatment Outcome; Vincristine

The objectives of this study were to evaluate the outcome after polychemotherapy for patients with primary cutaneous large-cell lymphomas (PCLL) and to validate the recently proposed immunohistologic classification of cutaneous lymphomas. Among 140 patients with positive skin biopsies included in the LNH87 protocol (for treatment of aggressive lymphomas), 49 patients met the criteria of PCLL. Characteristics were: sex ratio M/F, 2.3; age 18 to 83 years (median, 52), peripheral lymph nodes, n=22; diffuse disease, n=12; median tumor size, 4.5 cm; elevated lactate dehydrogenase, n=9; ECOG: 0/1, n=49. Histology was: follicular center B cell, n=23; B-lymphoblastic, n=1; anaplastic large-cell lymphoma, n=14 (T cell phenotype n=8); CD30- T cell lymphoma, n=11. All patients received polychemotherapy: under 70 years, ACVBP (three to four cycles and consolidation for 6 months) n=25; mBACOD (eight cycles) n=16; over 70 years, C(T)VP (six cycles) n=8. Radiation therapy was not included in the protocol. With a median follow-up of 5 years, 24/49 patients had relapsed, with 20 skin relapses. Event-free (EFS) and overall survival (OS) at 5 years were, respectively, 50 and 77%. Significant adverse prognostic factors were: histology (CD30- T cell lymphoma) and diffuse cutaneous disease (>10% of skin). The presence of nodal involvement was only significant for EFS. When compared to 140 non-cutaneous lymphoma patients included in the same trial and fully matched for the main clinical characteristics, OS was similar. In conclusion, PCLL behaves like other localized B or T cell extranodal lymphomas with the same prognostic factors (LDH, ECOG, age) except for CD30+ PCLL which have a very good prognosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Case-Control Studies; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; L-Lactate Dehydrogenase; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prednisone; Prognosis; Prospective Studies; Skin Neoplasms; Treatment Outcome; Vincristine; Vindesine

In the last few years, the search for new biologic markers in high-grade non-Hodgkin's lymphomas has provided important results. In particular, soluble CD30 (sCD30) levels were elevated in most patients with Hodgkin's disease (HD) and anaplastic large-cell lymphoma (ALCL).. From September 1988 to October 1993, treatment was completed in 70 previously untreated patients with ALCL, of whom 38 had the common type (ALCL-CT) and 32 had the Hodgkin's-like subtype (ALCL-HL). Serum sCD30 levels were measured at the time of diagnosis and after induction polychemotherapy in all patients; in addition, the initial sCD30 levels were compared with those obtained from 50 stage-matched patients with HD.. Pretreatment levels of sCD30 were highly elevated in the stage-matched group of HD patients compared with healthy controls; median sCD30 levels in patients with ALCL-CT and ALCL-HL were 18 and seven times higher, respectively, than in patients with HD. The sCD30 level normalized on achievement of complete response (CR). The risk of lower relapse-free survival was associated with bulky disease, advanced stage, and high pretreatment sCD30 levels; the risk of lower overall survival was associated with advanced stage and pretreatment levels of sCD30 in both univariate and multivariate analysis.. The results of this study suggest that sCD30 is a specific prognostic indicator of the risk for lower complete response rate and relapse-free expectancy for patients with ALCL.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Cytarabine; Doxorubicin; Female; Fluorouracil; Humans; Ki-1 Antigen; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Phenotype; Prednisone; Prognosis; Survival Analysis; Vincristine

Primary CNS lymphoma (PCNSL) and primary intraocular lymphoma (IOL) are usually treated with radiation therapy alone or in combination with chemotherapy. The neurotoxicity of these treatments can be substantial. This study attempts to define the toxicity and efficacy of the treatment of this disease with chemotherapy alone.. Fourteen nonimmunocompromised patients were accrued to a chemotherapy regimen that incorporated a 24-hour infusion of high-dose methotrexate total dose of 8.4 g/m2 with leucovorin rescue; thiotepa 35 mg/m2; vincristine 1.4 mg/m2; dexamethasone; and intrathecal cytarabine (Ara-C) and methotrexate (MTV) administered in 21-day cycles. Seven patients were prospectively followed up with formal neuropsychologic assessments for evidence of CNS toxicity.. The response rate was 100% with 11 (79%) complete responses and three (21%) partial responses. Cumulative survival and progression-free survival rates at more than 4.5 years were 68.8% and 34.3%, respectively. Median survival has not been reached, and median progression-free survival was 16.5 months. Toxicity included severe leukoencephalopathy that was clearly attributable to chemotherapy (two patients), grade 3 or 4 neutropenia in 50% of the cycles administered, ileus (one patient), and seizures (two patients). Mucositis and renal and hepatic toxicity were mild and not therapy limiting.. The MTV regimen is generally well tolerated and produces a high complete response rate. Chemotherapy alone should be investigated further in this disease to assess the necessity of initial radiation therapy, either alone or in combined modality regimens, for the achievement of optimal response and survival.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Cytarabine; Dexamethasone; Drug Administration Schedule; Eye Neoplasms; Female; Humans; Leucovorin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Pilot Projects; Thiotepa; Vincristine

The International Index is a powerful predictor of outcome in the aggressive non-Hodgkin's lymphomas that is based solely on clinical features. Proliferative activity (% S-phase) measured by flow cytometry has been reported to have prognostic significance in many series and may represent a biologic correlate of clinical behavior that further defines prognosis. Flow cytometric analysis of cellular DNA content and proliferative activity (% S-phase) was performed on fixed paraffin-embedded biopsy specimens from 242 previously untreated patients with diffuse, aggressive non-Hodgkin's lymphomas entered on phase III intergroup clinical trials. The International Index was calculated for each patient based on stage, lactate dehydrogenase, performance status, number of extranodal sites, and age, as previously reported. The International Index consistently predicted response to therapy (P = .027) and survival (P = .007) in this series. DNA aneuploidy was shown in 57% of cases, but was not predictive of clinical outcome. The median % S-phase was 9.9 (median coefficient of variation, 3.6%), which was highly correlated with mitotic index (P = .0001). Although a trend associating low proliferative activity with good early survival and very high S-phase with a shortened survival was shown, International Index risk was the only significant predictor of survival in the multivariate analysis. Although proliferative activity quantitated by flow cytometric analysis of nuclei extracted from paraffin-embedded specimens is probably predictive of survival, it is a less powerful prognostic indicator than clinical parameters represented by the International Index and provides no additional prognostic information.

Topics: Adult; Aged; Aneuploidy; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bleomycin; Cell Division; Cyclophosphamide; Cytarabine; Dexamethasone; DNA, Neoplasm; Doxorubicin; Etoposide; Female; Flow Cytometry; Humans; Leucovorin; Life Tables; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Neoplasm Staging; Prednisone; Prognosis; Severity of Illness Index; Survival Analysis; Treatment Outcome; Vincristine

We investigated whether Granulocyte colony-stimulating factor (G-CSF) could prevent myelotoxicity or accelerate hematopoietic recovery after intensive chemotherapy in previously untreated patients with diffuse large cell lymphoma (DLCL). Forty-two patients were included in a prospective clinical trial in which alternating chemotherapy ESAP (etoposide, Solu-Medrol, cytosine arabinoside, cis-platinum), m-BECOD (low doses methotrexate, bleomycin, epirubicin, cyclophosphamide, vincristine, dexamethasone), MVPP-Bleo (mitoxantrone, vincristine, prednisone, procarbazine, bleomycin) were administered by 9 cycles. Each cycle was followed by 10 days of G-CSF (5 micrograms/kg/day) started five days after chemotherapy compared to a control group which received chemotherapy without G-CSF support. Leucocytes and granulocytes were significantly higher in patients receiving G-CSF compared to the control group. The total number of days of leukopenia (WBC counts below 2.0 x 10(9)/L and absolute granulocytes below 1.0 x 10(9)/L) were longer in the patients without G-CSF compared to those who received G-CSF (14.1 days versus 1.9 days). Delays in treatment were most frequent in the control group: 38% versus 4% in all cycles. Infection episodes occurred in 41 out of 168 cycles (25%) in the control group compared to 7 out of 172 (4%) in the G-CSF arm. Complete response was achieved in 12 out of 22 (54%) in the control group compared to 16 out 20 (80%) in the patients who received G-CSF. Toxicity secondary to G-CSF was mild. G-CSF can be administered safely to patients with DLCL and results in improved hematologic recovery after intensive chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Diseases; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Epirubicin; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunologic Factors; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Methylprednisolone; Middle Aged; Mitoxantrone; Prednisone; Procarbazine; Prospective Studies; Treatment Outcome; Vincristine

In patients with diffuse large cell lymphoma treated with chemotherapy the presence of high levels of serum beta 2 microglobulin has been considered as a bad prognostic factor. Until now, attempts to detect early relapse in patients with diffuse large cell lymphoma have been sparse. To address this issue we began a prospective clinical trial to evaluate the role of different clinical, laboratory and radiographic tests in the detection of early relapse in non-Hodgkin's lymphoma (NHL). Only serum beta 2 microglobulin levels had clinical significance and 26 of 53 patients (49%) had abnormal levels, 3 to 23.1 months (mean 8.5 months) before evident relapse. Elevated serum lactic dehydrogenase (LDH) levels and beta 2 microglobulin were observed in six patients and all relapsed, suggesting that the combination of these two tests should be considered in future prospective clinical trials in order to define the utility of both tests to detect early relapse. This information may allow us to begin chemotherapy when the tumor mass is still low thereby making the probability of achieving a long second remission more likely.

Topics: Antineoplastic Combined Chemotherapy Protocols; beta 2-Microglobulin; Biomarkers, Tumor; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Follow-Up Studies; Humans; L-Lactate Dehydrogenase; Leucovorin; Life Tables; Lymphoma, Large B-Cell, Diffuse; Methotrexate; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Predictive Value of Tests; Prospective Studies; Remission Induction; Survival Analysis; Vincristine

The prognosis of advanced-stage diffuse large-cell lymphoma (DLCL) has improved with the use of the third-generation regimens such as methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B). However, different results have been reported. Therefore, we started a cooperative study to confirm the efficacy of MACOP-B. An analysis of prognostic factors was also performed to identify poor-prognosis patients.. Between June 1986 and March 1989, 180 patients with advanced-stage DLCL were treated with MACOP-B. MACOP-B was given according to the original scheme. Numerous clinical features possibly predictive for complete response (CR), disease-free survival (DFS), and survival were analyzed in univariate and multivariate analyses.. One hundred twenty-seven patients (71%) achieved a complete remission, 20 (11%) achieved a partial remission, 24 (13%) had unchanged or progressive disease, and nine (5%) died due to toxicity. With a median follow-up of 28 months, 71% of 127 CRs remain in first remission. Predicted 3-year survival for all 180 patients is 60%, and 3-year DFS for the 127 CRs is 67%. Overall toxicity was acceptable, with mucositis being the most frequent severe side effect. A multivariate regression analysis identified lactate dehydrogenase (LDH) level, bone marrow involvement, and tumor burden as independent risk factors for survival. These factors were also important for achievement of remission and DFS and allowed us to identify three distinct risk groups of patients with good, intermediate, and poor prognosis, with 3-year survival rates of 80%, 59%, and %29, respectively.. These results confirm the effectiveness of MACOP-B in advanced-stage DLCL at low or intermediate risk; however, high-risk patients are in urgent need of new therapeutic approaches. A better definition of prognostic features would allow a more reliable comparison of different treatment regimens, as well as an effective tailoring of therapy by prognostic groups.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Multivariate Analysis; Prednisone; Prognosis; Regression Analysis; Risk Factors; Survival Analysis; Vincristine

Nine adult patients with Ki-1-positive large-cell anaplastic lymphoma were treated with MACOP-B. Two suffered from relapsed disease and had previously received chemotherapy; a third patient had received a single dose of 100 mg/m2 cisplatin before initiation of MACOP-B. The stage of lymphoma was determined according to the Ann Arbor Conference criteria and was II in one, III in two and IV in six patients. All patients had constitutional symptoms. Five patients had achieved complete remission 4 weeks after termination of the protocol and there were two partial remissions. One patient died of massive pulmonary embolism during the 4th week of treatment; another patient, who had received MACOP-B as salvage therapy, died of progressive lymphoma 1 month after completion of the regimen. Maximal observed toxicities according to WHO were mucositis grade 3 (n = 3) and there were three cases with thromboembolic complications, including a fatal pulmonary embolism in a young patient. However, MACOP-B appears an effective, fairly well-tolerated and feasible therapy for patients with Ki-1-positive large-cell anaplastic lymphoma.

Topics: Adult; Aged; Antigens, CD; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Neoplasms; Cyclophosphamide; Doxorubicin; Female; Humans; Ki-1 Antigen; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Prednisone; Remission Induction; Vincristine

Fifty patients with advanced (Stage III and IV) large cell and immunoblastic lymphoma were treated with eight 4-week courses of chemotherapy. The first two identical A courses were composed of high dose cyclophosphamide, vincristine, 5-day administration of bleomycin, 2-week prednisone, and methotrexate with calcium leucovorin. The next two "B" courses were composed of vincristine, 3-day administration of doxorubicin together with bleomycin, and prednisone. The next two "C" courses were composed of cyclophosphamide, vincristine, bleomycin, prednisone, methotrexate, and calcium leucovorin. The last two "D" courses were the same as "B" courses. CNS prophylaxis was done with intrathecal methotrexate. Fourty-two patients (84%) achieved complete remission, 7 patients entered partial remission, and 1 patient failed to respond. The median survival of all groups was 80 + months (range 2-181 + months). Nine patients relapsed (21%), and seven patients died in complete remission, three of them died of toxicity. The most frequent toxicity was myelosuppression, mostly leukopenia, frequently followed by infection, sometimes severe. Neurotoxicity and stomatitis were frequent, but usually not severe. Two patients developed secondary malignancies. Most of the patients (54%) are alive without evidence of disease at present.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Male; Methotrexate; Middle Aged; Prednisone; Vincristine

In 1984, the Eastern Cooperative Oncology Group began a randomized controlled clinical trial of patients with advanced (stage III or IV) diffuse mixed or diffuse large-cell lymphoma to determine whether complete-remission rates, survival, and toxicity differed when patients were treated with a chemotherapeutic regimen containing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), as compared with a regimen containing bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone, methotrexate, and leucovorin (m-BACOD).. From July 1984 through January 1988, 392 patients were enrolled, 325 of whom (83 percent) were eligible for the analysis and capable of being evaluated. The extent of disease was defined according to standard staging techniques, including bilateral bone-core biopsies in 88 percent of patients. Randomization was stratified according to age (< 60 or > or = 60 years), performance status (0, 1, or other), stage (III or IV), and histologic presentation (diffuse mixed or diffuse large-cell lymphoma).. After a median follow-up of four years, there were no significant differences in rates of complete remission, time to treatment failure, disease-free survival, or overall survival in the patients treated with CHOP as compared with those treated with m-BACOD. However, there was more severe and life-threatening pulmonary, infectious, and hematologic toxicity associated with the m-BACOD regimen. In an attempt to measure the importance of dose intensity in the 325 patients who could be analyzed, we retrospectively calculated dose intensity (measured in milligrams per square meter of body-surface area per week) and normalized dose intensity (defined as a percentage of the prescribed dose) for all drugs. The median normalized dose intensity for both cyclophosphamide and doxorubicin was found to be greater in the patients treated with CHOP than in those treated with m-BACOD.. For patients with stage III or IV diffuse mixed or diffuse large-cell lymphoma, CHOP is superior to m-BACOD, but the role of dose intensity is not yet clear.

Topics: Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prednisone; Remission Induction; Survival Rate; Vincristine

Eighty-one patients with large-cell non-Hodgkin's lymphoma achieving complete restaging verified remission after induction chemotherapy (CHOP-Bleo or m-BACOD) were randomized to the following 3 arms: 1. No further treatment (observation). 2. Early consolidation therapy with 6 courses of CVP (cyclophosphamide, vincristine, prednisone) given monthly. 3. Maintenance therapy with cyclophosphamide and prednisone given every 6 weeks for 2 years. The relapse-free survival was better in the maintenance and consolidation arms than in the observation arm. The additional therapy given after the initial complete remission produced lasting disease control in a considerable number of patients and with acceptable toxicity. The authors feel that patients with large-cell lymphoma do not need more aggressive and toxic initial management because the use of maintenance therapy can increase the number of patients remaining in complete remission by more conventional, less toxic chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Prednisone; Proportional Hazards Models; Survival Analysis; Vincristine

One hundred thirty-four assessable patients with stage II-IV large-cell lymphoma (LCL) were treated with the combination chemotherapy regimen methotrexate with leucovorin, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) between July 1981 and May 1986. The m-BACOD regimen substituted moderate-dose methotrexate (200 mg/m2 x 2) for the high-dose methotrexate used in the preceding M-BACOD regimen; all other drugs were administered as with m-BACOD. Eighty-two patients (61%) in the completed m-BACOD trial achieved a complete response (CR). With a median follow-up of 3.6 years, 62 patients (76%) continue in CR. Predicted survivals of 1, 3, and 5 years for the entire m-BACOD group are 80%, 63%, and 60%, respectively, with a 5-year disease-free survival (DFS) of 74% for the patients who achieve CR. The results obtained with m-BACOD are comparable with those obtained in the preceding M-BACOD trial, which now has a median follow-up of 8.0 years. The reduction in methotrexate dosage in m-BACOD patients was not associated with an increased incidence of CNS relapse. Long-term follow-up of the 215 M/m-BACOD patients indicates that the regimens are not associated with an increased incidence of secondary malignancy. Prolonged follow-up also indicates that advanced-stage patients have a persistent rate of late relapse of about 7.0% per year for years 2 to 5 of their follow-up and that stage II patients have an approximate 2.1% per year rate of late relapse. Application of the previously described prognostic factor model to the 215 M/m-BACOD patients from the completed trials identifies a high-risk group of patients with a CR rate and predicted 5-year survival (38% and 24%, respectively) that are significantly worse than those of the group as a whole (65% and 57%, respectively).

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Central Nervous System Diseases; Clinical Trials as Topic; Cyclophosphamide; Dexamethasone; Dose-Response Relationship, Drug; Doxorubicin; Follow-Up Studies; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Methotrexate; Neoplasm Recurrence, Local; Prognosis; Remission Induction; Survival Analysis; Time Factors; Vincristine

In 1976 we began a randomized study for the treatment of patients with stage III and IV diffuse histiocytic lymphoma. The therapy was either ACOMLA (doxorubicin, cyclophosphamide, vincristine [oncovin], methotrexate with leucovorin rescue, and cytarabine) or CHOP-B (cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristine [oncovin], prednisone, and bleomycin). A complete response (CR) was achieved in 13 (65%) of 20 patients treated with ACOMLA and in 20 (71%) of the 28 patients treated with CHOP-B. Four patients achieving CR with ACOMLA and three patients treated with CHOP-B have relapsed for an overall relapse rate of 21%. Partial response (PR) was obtained in four patients treated with ACOMLA and five patients treated with CHOP-B. Median follow-up time is 36 months for the combined treatment groups. Multiple regression analysis demonstrated that those patients who were classified by the Lukes-Collins criteria as having histiocytic lymphoma not of follicular center-cell origin (combined T- and B-cell immunoblastic sarcoma) had a significantly worse survival as compared to patients classified with follicular center-cell origin lymphoma (large cell noncleaved, large cell cleaved, and large cell unclassified) with a 40% five-year survival versus an 80% five-year survival (P = .011). The CR rate however for these two large categories of patients was 63% v 73% respectively, and the relapse rates were equivalent. The increased survival in the follicular center-cell origin lymphomas may be related to a longer survival of PRs and relapsed patients as compared to the patients with nonfollicular center-cell lymphomas.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Doxorubicin; Female; Follow-Up Studies; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Prednisone; Prognosis; Random Allocation; Recurrence; Time Factors; Vincristine

Two combination chemotherapy programs, ACOMLA (doxorubicin, cyclophosphamide, vincristine, methotrexate and leucovorin rescue, and cytarabine) and CHOP-B (cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin), were evaluated in 29 prospective randomized patients with advanced diffuse histiocytic lymphoma. A complete response was achieved in 13 of the 15 patients (87%) treated with CHOP-B and in nine of the 14 patients (64%) treated with ACOMLA. The overall complete response rate was 75%. Two patients treated with ACOMLA and none of the CHOP-B-treated patients have relapsed. Median followup is 32 months for ACOMLA patients and 26 months for CHOP-B patients. Actuarial freedom from relapse at 2 years is 49.9% for ACOMLA and 93.3% for CHOP-B (P = 0.04). Toxicity was substantial, with eight nonfatal episodes of sepsis and three drug-related deaths. There have been no central nervous system relapses. Although patients treated with CHOP-B have a better response rate, the small numbers of patients treated to date preclude definitive conclusions.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Therapy, Combination; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Methotrexate; Prednisone; Prognosis; Random Allocation; Vincristine

Topics: Adult; Aged; Antineoplastic Agents; Bone Marrow; Burkitt Lymphoma; Child; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Leucovorin; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prognosis; Remission, Spontaneous; Time Factors

Thirty patients with diffuse histiocytic lymphoma (DHL) were treated with one of three regimens that included cyclophosphamide, vincristine, methotrexate with citrovorum factor rescue, and cytosine arabinoside. Twelve patients had a complete response with a predicted 50% survival of at least 76 months. The medium survival of the 11 partial responders and seven nonresponders was 18 and 6 months, respectively. The addition of methotrexate and cytosine arabinoside may have a beneficial effect in therapy for DHL. From analysis of these results, there is reason to believe that efficacy may be partially dependent on the scheduling and dose of these two drugs.

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Recurrence; Remission, Spontaneous; Time Factors; Vincristine

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System; Cerebrospinal Fluid; Chemical and Drug Induced Liver Injury; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Female; Humans; Kaplan-Meier Estimate; Kidney Diseases; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Mucositis; Neoplasm Invasiveness; Prednisone; Proportional Hazards Models; Prospective Studies; Recurrence; Rituximab; Vincristine

The purpose of this study is to investigate the most suitable first-line approach and the best combination treatment for primary mediastinal large B-cell lymphoma (PMLBCL) as they have been matter of debate for at least two decades.. Our single centre experience in the treatment of 98 de novo PMLBCL patients over the last 20 years is reviewed. All patients received MACOP-B chemotherapy. Thirty-seven received both rituximab and mediastinal radiotherapy; 30 were irradiated after chemotherapy, although not receiving rituximab and 20 received rituximab without radiotherapy consolidation. Eleven patients received chemotherapy only.. Sixty-one (62.2%) patients achieved a complete response after MACOP-B (with or without rituximab); among the 27 (27.6%) partial responders, 21 obtained a complete response after radiotherapy. At the end of their scheduled treatment, 82 patients (83.7%) had a complete and 6 a partial response (6.1%). Eleven patients relapsed within the first 2 years of follow-up. The 17-year overall survival is 72.0% (15 patients died); progression-free and disease-free survival are 67.6% and 88.4%, respectively. A statistically significant difference in overall and progression-free survival was noted among treatment groups, although no disease-free survival difference was documented.. Our data indicate that a third-generation regimen like MACOP-B could be considered a suitable first-line treatment. Mediastinal consolidation radiotherapy impacts on survival and complete response rates and remains a good strategy to convert partial into complete responses. Data suggest that radiotherapy may be avoided in patients obtaining a complete response after (immuno)chemotherapy, but this requires confirmation with further ad hoc studies.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Humans; Immunotherapy; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Mediastinal Neoplasms; Methotrexate; Middle Aged; Neoplasm Staging; Prednisone; Retrospective Studies; Rituximab; Vincristine; Young Adult

Topics: Adenocarcinoma; Adult; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colonic Neoplasms; Cyclophosphamide; Doxorubicin; Fluorouracil; Humans; Hyperpigmentation; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Organoplatinum Compounds; Prednisone; Rituximab; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain; Central Nervous System Neoplasms; Child, Preschool; Combined Modality Therapy; Cranial Irradiation; Cyclophosphamide; Cytarabine; Demyelinating Diseases; Diagnosis, Differential; Doxorubicin; Encephalomyelitis, Acute Disseminated; Etoposide; Humans; Hydrocortisone; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Magnetic Resonance Imaging; Male; Methotrexate; Prednisone; Vincristine

To explore the clinical and prognostic features as well as treatment response of childhood B-cell non-Hodgkin's lymphoma/acute lymphoblastic leukemia (B-NHL/B-ALL), so as to better modify the treatment for further improving the prognosis.. The clinical data of 43 patients with newly-diagnosed childhood B-NHL/B-ALL from July 2005 to December 2013 in West China Second Hospital of Sichuan University were retrospectively analyzed with particular focus on clinical presentations, laboratory findings and histology. Among them 26 patients received B-NHL-2010 protocol and 17 patients received LMB-89 protocol treatment. Kaplan-Meier method was used to compare the survival rates between groups, while multiple factor logistic regression was used to identify the prognostic factors.. (1) The median age at diagnosis was 7.58 (2.42-13.67) years. The male-to-female ratio was 2.9 : 1. No significant difference was found in the median age at diagnosis between male and female children with B-NHL/B-ALL (P = 0.837). (2) Burkitt's lymphoma was the most common (34/43, 79.07%), followed by diffuse large B cell lymphoma (4/43, 9.3%), ALL-L3 (3/43, 6.98%) and others (2/43, 4.65%) in decreasing frequency. (3) According to St. Jude staging classification, 4 patients (9.30%) were divided into stage I, 9 patients (20.93%) into stage II, 23 patients (53.49%) into stage III and 7 patients (16.28%) into stage IV; (4) Clinically, the common predilection sites were as following: ileocecus (11/43, 25.58%), nasopharynx (10/43, 23.26%), faciomaxillary (9/43, 20.93%), superficial lymphadenopathy (8/43, 18.60%), other sites such as mediastinum and bone marrow (5/43, 11.63%). (5) With a median follow up of 24 months (0.7-105 months), the 2-year overall survival (OS) rate and event-free survival (EFS) rate were 79.8% ± 6.5%% and 71.0% ± 7.2%, respectively. The 2-year OS and EFS rates in patients treated with B-NHL-2010 protocol were 79.1% ± 8.4% and 74.1% ± 8.4%, while those in patients treated with LMB-89 protocol were 87.5% ± 8.3% and 66.7% ± 12.4%, respectively, but there was no significant difference between them (P > 0.05). The 2-year EFS rate in patients with LDH > 2N and bone marrow infiltration were significantly lower than that of other groups (P < 0.05). (6) 8 patients (18.6%) relapsed. The median relapsed time was 6 months (2-9 months). 1 patient suffered progressive disease. Male, systemic symptom, elevated LDH, bone marrow and CNS infiltration and advanced stage (stage III and stage IV) were associated with relapse /progressive disease. Logistic regression analysis showed that LDH > 2N was an independent unfavorable prognostic factors (OR = 31.129, P = 0.02).. Outcome of B-NHL/B-ALL is greatly improved by current intensive and short-time chemotherapy regimen. The 2-year event-free survival (EFS) rate is 71.0% ± 7.2%. There is no significant difference in EFS rate between patients treated with B-NHL-2010 protocol and LMB89 protocol. The long-term survival rate in patient with advanced disease need to be further improved.

Topics: Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Child; Cyclophosphamide; Cytarabine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Humans; Hydrocortisone; Leucovorin; Logistic Models; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Multivariate Analysis; Neoplasm Staging; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Prognosis; Retrospective Studies; Survival Rate; Vincristine

Central nervous system (CNS) relapse continues to be a frequent and usually fatal complication in patients with diffuse large B cell lymphoma (DLBCL). Multiple factors identify the possibility of relapse and justify neurological prophylaxis; however, most of these have not been confirmed. Thus, the use of prophylaxis has not been defined. From 1988 to 2008, 3,258 patients with DLBCL with higher clinical risks and multiple extranodal involvement that have been treated with standard anthracycline-based chemotherapy: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP-R (CHOP plus rituximab) and that achieve complete response were retrospectively analyzed to assess the efficacy of CNS prophylaxis. One thousand five patients received different schedules for CNS prophylaxis, and 2,253 patients did not receive CNS prophylaxis. CNS relapse was similar in patients who receive prophylaxis (6 %) compared to patients who did not receive prophylaxis (5.9 %). Overall survival of patients who either receive or did not receive prophylaxis was not statistically significant: 49 % versus 53 % (p = 0.802). Thus, it seems that CNS prophylaxis did not improve outcome in this special setting of patients, and no prognostic factors to predict the presence of CNS relapse were identified. It is evident that multicentric studies are necessary to define the role of prophylaxis in order to prevent CNS relapse and that the therapeutic procedure will be carefully revised.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cancer Care Facilities; Central Nervous System Neoplasms; Combined Modality Therapy; Cytarabine; Female; Follow-Up Studies; Humans; Hydrocortisone; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged

Third-generation regimens (MACOP-B [methotrexate/leucovorin (LV)/doxorubicin/cyclophosphamide/vincristine/ prednisone/bleomycin] or VACOP-B [etoposide/LV/doxorubicin/cyclophosphamide/vincristine/prednisone/bleomycin]) in combination with local radiation therapy seem to improve lymphoma-free survival of primary mediastinal large B-cell lymphoma (PMLBCL). Recently, the superiority of R-CHOP (rituximab plus cyclophosphamide/doxorubicin/vincristine/ prednisone) over CHOP-like regimens has been demonstrated in elderly and younger patients with low-risk diffuse large B-cell lymphoma.. Retrospectively, between February 2002 and July 2006, 45 previously untreated patients with PMLBCL were treated with a combination of a third-generation chemotherapy regimen (MACOP-B or VACOP-B), concurrent rituximab, and mediastinal radiation therapy.. Twenty-six (62%) patients achieved a complete response (CR), and 15 (36%) obtained a partial response after MACOP-B/VACOP-B plus rituximab. After radiation therapy, the CR rate was 80%. At a median follow-up of 28 months, among the 34 patients who obtained a CR, 3 relapsed after 16, 19, and 22 months, respectively. Projected overall survival was 80% at 5 years; the relapse-free survival (RFS) curve of the 34 patients who achieved CR was 88% at 5 years.. In this retrospective study, in patients with PMLBCL, combined-modality treatment using the MACOP-B/VACOP-B regimen plus rituximab induces a high remission rate, with patients having a > 80% chance of surviving relapse free at 5 years. In comparison with historical data on MACOP-B/VACOP-B without rituximab, there are no statistically significant differences in terms of CR and RFS rates.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Etoposide; Female; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Mediastinal Neoplasms; Methotrexate; Middle Aged; Prednisone; Radiotherapy, Adjuvant; Retrospective Studies; Rituximab; Survival Rate; Treatment Outcome; Vincristine; Young Adult

Primary breast lymphoma (PBL) is a rare form of extranodal non-Hodgkin's lymphoma (NHL), whose own specific biological characteristics still need to be fully defined. No significant prognostic factor has been found and the optimal therapeutic strategy is uncertain. However, an intensified systemic therapy has been advocated to prevent relapse, even in patients who show a complete response to local treatment. We report two cases of primary diffuse large B-cell breast lymphoma, review the literature about this topic, and discuss treatment options. We conclude that differential therapeutic strategies based on the risk of relapse associated with the International Prognostic Index (IPI) are a reasonable way to approach PBL, and can avoid undue toxicity deriving from treatment.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Breast; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Female; Humans; Immunohistochemistry; Injections, Spinal; L-Lactate Dehydrogenase; Leucovorin; Leukocyte Common Antigens; Lymphoma, Large B-Cell, Diffuse; Mastectomy, Segmental; Methotrexate; Neoplasm Staging; Prednisone; Rituximab; Vincristine

The case of a 16-year-old girl with primary mediastinal large B-cell lymphoma who had thrombosis in the brachiocephalic, subclavian, and internal jugular veins at presentation is reported. MACOP-B chemotherapy plus radiation therapy could be the first-line strategy, but MACOP-B increases the risk of thrombosis. Although an effective method for initial treatment of venous thromboembolism (VTE) in cancer patients has not been established, recent studies revealed that the administration of a low-molecular-weight heparin (LMWH) was effective for secondary prevention of VTE. Therefore, the patient in this case was treated with MACOP-B plus rituximab followed by radiation therapy, and an LMWH was administered through the course of treatment. She achieved complete remission and never suffered from VTE. This case suggests that long-term administration of an LMWH contributes to the primary improvement and secondary prevention of VTE even in patients who are at high risk for thrombosis.

Topics: Adolescent; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Heparin, Low-Molecular-Weight; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Mediastinal Neoplasms; Methotrexate; Prednisone; Rituximab; Venous Thromboembolism; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Methotrexate; Prognosis; Treatment Outcome; Vincristine

Common methylenetetrahydrofolate reductase gene variants (MTHFR C677T and A1298C) have been described to have opposite effects on cancer patients. They may reduce cancer susceptibility and increase drug-related toxicity when folate antagonists (e.g. methotrexate) are utilized. We analyzed 110 patients with high-grade non-Hodgkin's lymphoma (NHL), 68 of whom were eligible for a chemotherapy combination containing methotrexate (MACOP-B) and 42 for chemotherapy without methotrexate (CHOP).. Patients were genotyped by polymerase chain reaction and stratified by MTHFR variants. These data were related to the toxicity (WHO grade GO-4) that the patients suffered and their survival. Overall 64 cases (58.2%) developed some form of toxicity and 23 (20.9%) had grade 3/4 toxicity.. When considering toxicity of any grade (grade 1-4), the 677TT genotype was significantly over-represented among cases with mucositis (OR=4.85; 95% CI, 1.47-15.97; p=0.009) and those with hepatic toxicity (OR=3.43; 95% CI, 0.99-11.86; p=0.052). Sub-analyses in the group treated with MACOP-B showed a slight increase in the risk of developing mucositis (OR=5.22; 95% CI, 1.20-27.27; p=0.03), and a strong increase in the risk of hepatic toxicity (OR=7.08; 95% CI, 1.38-36.2; p=0.019) and thrombocytopenia (OR=7.69, 95% CI 1.0-58.94; p=0.05). Interestingly, compared to the risk of developing toxicity of any grade, the risk of developing severe (grade 3/4) mucositis was almost doubled in the whole group of cases with 677TT (OR=8.13; 95% CI 1.61-41.04; p=0.011) and dramatically increased in the MACOP-B-treated cases with this gene variant (OR=24.6; 95% CI 2.49-87.41; p=0.001). There were significant results for 1298CC cases exclusively for mucositis (any grade, OR=5.33; 95% CI, 1.25-22.70; p=0.023 and OR=9.15; 95% CI, 1.14-73.41; p=0.037; for the whole group and the MACOP-B-treated group, respectively). Similarly, the risk of 1298CC patients developing severe mucositis increased (OR=9.24; 95% CI, 1.47-58.0; p=0.017 and OR=11.53; 0.93-143.18; p=0.057; in the whole group and in the MACOP-B-treated group, respectively). Event-free survival analysis revealed a lower probability of event-free survival at 5 years for 677T-carriers (log-ranks, p=0.05 and p=0.07 in the whole group and in the MACOP-B-treated group, respectively). More significant results were obtained when 1298CC cases were excluded from the reference group (log-ranks, p=0.03 and p=0.04, respectively). No significant associations were found in the CHOP-treated group.. Our data suggest that MTHFR gene variants play a critical role in NHL outcome, possibly by interfering with the action of methotrexate with significant effects on toxicity and survival. Genotyping of folate pathway gene variants might be useful to enable reduction of chemotherapy toxicity and/or to improve survival by indicating when dose adjustments or alternative treatments are necessary.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amino Acid Substitution; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chemical and Drug Induced Liver Injury; Cyclophosphamide; Doxorubicin; Female; Genotype; Hematologic Diseases; Humans; Kaplan-Meier Estimate; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mucositis; Neoplasm Proteins; Polymorphism, Single Nucleotide; Prednisone; Risk; Survival Analysis; Treatment Outcome; Vincristine

Anaplastic large cell lymphoma (ALCL) is 1 of 17 mature T cell neoplasms described by the World Health Organization. Primary central nervous system (PCNS) ALCL represents a distinct rare form of this family of non-Hodgkin lymphoma and discussions of prognosis and management are limited to case reports and case series. Therapies for this disease largely parallel that of other PCNS lymphomas. We report the case of a 38-year-old male soldier who presented with a parieto-occipital mass lesion and neurological sequelae without evidence of systemic disease. Pathologic evaluation of tissue from brain biopsy confirmed ALCL. We elected treatment with an intensive combination of systemic and intrathecal chemotherapy with radiotherapy. Our patient is in complete remission 15 months following therapy. Tailored therapies for PCNS ALCL are unavailable and this regimen may be an option for patients who can tolerate intensive treatments.

Topics: Adult; Antineoplastic Agents; Central Nervous System Neoplasms; Combined Modality Therapy; Dexamethasone; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Procarbazine; Vincristine

Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct clinico-pathological subtype of diffuse large B-cell lymphoma (DLBCL). The optimal treatment is unknown, with some studies suggesting a superior outcome with dose-intensive chemotherapy regimens, and the role of radiotherapy remains ill-defined.. The British Columbia Cancer Agency lymphoma database was searched and records reviewed to identify those patients presenting with a prominent mediastinal mass and considered to be PMBCL based on the current REAL/WHO classifications. Patients were treated based on era-specific BCCA guidelines (1980-1992 MACOPB/VACOPB; 1992-2001 CHOP-type; 2001-present CHOP-R). Beginning in January 1998 involved-field radiotherapy was recommended to be routinely administered following chemotherapy. Prior to this, use of radiotherapy was individualized in advanced disease.. In total, 153 patients with newly diagnosed PMBCL were identified between 28 July 1980 and 30 June 2003. The median age was 37 years (range 13-82) and the majority had stage I/II (74%), bulky mediastinal disease (75%). Overall (OS) and progression-free (PFS) survival at 5 years for the entire cohort were 75% and 69%, respectively. In direct comparison with a cohort of patients with DLBCL (n = 1273), OS (P = 10(-4)) and PFS (P = 0.0001) favored PMBCL. The age-adjusted International Prognostic Index (aaIPI) was not predictive of survival (P = 0.18). Five-year OS in patients < 65 years old treated with MACOPB/VACOPB, CHOP-R and CHOP-type was 87%, 81% and 71% respectively (P = 0.048). In pair-wise survival comparisons, only MACOPB/VACOPB and CHOP-type treated patients were significantly different (P = 0.016). In Cox multiple regression analysis, poor performance status remained the only predictor of survival, with treatment received demonstrating a trend to worse outcome for patients treated with CHOP-type regimens (P = 0.09). In an intention-to-treat analysis comparing the era before radiotherapy was routinely administered with after, there was no significant difference in 5-year PFS (74% versus 62%; P = 0.09) or OS (78% versus 69%; P = 0.14).. In this single institution, population-based retrospective study, we found that PMBCL patients have excellent survival rates and a distinct plateau is observed in PFS, in striking comparison to DLBCL. The aaIPI was not predictive of survival in this population, suggesting that other prognostic models may be better suited for risk stratification. Dose-intensified chemotherapy with MACOPB or VACOPB demonstrated a trend to superior outcome over CHOP-type chemotherapy. However, further randomized studies are needed and the impact of rituximab on these comparisons must be considered. Finally, the routine addition of radiotherapy does not improve survival.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; British Columbia; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Leucovorin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Mediastinal Neoplasms; Methotrexate; Middle Aged; Prednisone; Prognosis; Retrospective Studies; Survival Rate; Treatment Outcome; Vincristine

To compare outcomes of patients with HIV-Burkitt's lymphoma (HIV-BL) and HIV-diffuse large-cell lymphoma (HIV-DLCL) after treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or M-BACOD (methotrexate, bleomycin, cyclophosphamide, etoposide) in pre-highly active antiretroviral therapy (HAART) versus HAART eras.. Three hundred sixty-three patients with AIDS-related lymphoma diagnosed from 1982 to 2003 were reviewed retrospectively, including 262 in the pre-HAART (HIV-BL, 117; HIV-DLCL, 145) and 101 in the HAART era (HIV-BL, 18; HIV-DLCL, 83). Pre-HAART included those who did not receive HAART, and HAART era included those diagnosed after January 1997 who received HAART.. There were no significant differences between groups in terms of age, sex, history of injection drug use, prior AIDS, lactate dehydrogenase level, and disease stage at diagnosis. Compared with HIV-BL, HIV-DLCL was associated with significantly lower CD4 counts in the pre-HAART but not the HAART era. Although the overall median survival was similar for both groups in the pre-HAART era (HIV-BL, 6.4 months v HIV-DLCL, 8.3 months; P = .43), survival was significantly worse in patients with HIV-BL in the HAART era (HIV-BL, 5.7 months v HIV-DLCL, 43.2 months; P = .0003). Failure to attain complete remission and CD4 count less than 100 cells/mm(3) independently predicted for poor survival in the pre-HAART era. In comparison, histology of HIV-BL and no attainment of complete remission were independent poor prognostic factors in the HAART era.. Survival of patients with HIV-DLCL has improved in the HAART era, along with CD4 count, whereas survival of similarly treated patients with HIV-BL remained poor. The current practice of using the same regimen for both groups of patients should be re-evaluated.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Bleomycin; Burkitt Lymphoma; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, AIDS-Related; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Prednisone; Retrospective Studies; Survival Rate; Treatment Outcome; Vincristine

Primary lacrimal sac lymphoma is extremely rare in children. To our knowledge, only two previous cases have been reported in the literature. Here, we report the case of a 9-year-old girl with primary lacrimal sac lymphoma who has recurrent mass.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Eye Neoplasms; Female; Humans; Hydrocortisone; Hyperplasia; Lacrimal Apparatus; Leucovorin; Lymph Nodes; Lymphoma, Large B-Cell, Diffuse; Methotrexate; Prednisone; Vincristine

To evaluate efficacy of treatment of primary mediastinal B-cell lymphosarcoma (PMBLS).. Fifty nine patients with PMBLD were divided into three groups. Group 1 (n = 15) received 8 courses of CHOP, prevention of neuroleukemia and radiotherapy (RT). Group 2 (n = 8)--4 courses of ProMACE-CytaBOM or 1 course of MACOP-B, prevention of neuroleukemia and RT. Group 3 (n = 36)--2 courses of CHOP and 2-3 courses of ESHAP or 3 courses of DexaBEAM, surgical removal of residual mediastinal tumor (RMT), RT.. The number of complete remissions in group 1 and 2 was the same (26 and 25%, respectively). Overall 5-year and event-free survivals in groups 1 and 2 were 52 +/- 5 and 13 +/- 5; 62 +/- 5 and 38 +/- 8%, respectively. In group 3 a complete remission was observed in 89% patients (p = 0.01), overall 5-year and event-free survival reached 88 +/- 8 and 85 +/- 7%, respectively. Removal of RMT in time of tumor size stabilization and partial remission (in 12 of 15 cases) led to a complete remission but in progression of the disease (in 3 cases) appeared ineffective. RT resulted in complete remission in 39 of 53 cases, stabilization of tumor growth was in 3 cases, progression--in 10, recurrence--in 1. RT was ineffective in all 4 cases of partial remission. RT use in stabilization of tumor size induced complete remission only in 1 of 7 cases.. CHOP program is ineffective in PMBLS. Program ProMACE-CytaBOM or MACOP-B is insignificantly more effective than CHOP. Combined therapy is most effective. Surgery is justified in partial remission and tumor growth arrest. RT is indicated in complete remission to achieve its consolidation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Humans; Leucovorin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Mediastinal Neoplasms; Methotrexate; Prednisone; Remission Induction; Vincristine

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Resistance, Neoplasm; Etoposide; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Mitoxantrone; Orchiectomy; Prednisone; Recurrence; Remission Induction; Rituximab; Skin Neoplasms; Testis; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Child; Colonoscopy; Cyclophosphamide; Doxorubicin; Gastrointestinal Hemorrhage; Humans; Hydrocortisone; Immunophenotyping; Intestinal Mucosa; Intestinal Polyps; Leucovorin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Methylprednisolone; Rectum; Vincristine

We report a rare complication of a secondary malignant solid tumor in two patients with non-Hodgkin's malignant lymphoma who developed lung adenocarcinoma after treatments with combination chemotherapies. The first was a case of primary malignant lymphoma of the cervical spinal cord which had been previously treated with radiation to the spinal lesion and combination chemotherapies and entered complete remission. The patient was further treated for relapse with autologous bone marrow transplantation preconditioned with high-dose chemotherapy. Lung adenocarcinoma developed 5.5 years after the initial diagnosis. The second case of malignant lymphoma of lymph nodes did not respond to conventional combination chemotherapies and did not enter remission. Lung adenocarcinoma developed 1 year after the initial diagnosis. The two patients died of lung carcinoma. The clinical profiles of these cases are presented and the causal relationship of primary malignant neoplasms to the second malignant neoplasms is discussed.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Drug Administration Schedule; Female; Humans; Leucovorin; Lung Neoplasms; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Neoplasms, Second Primary; Prednisone; Spinal Cord Neoplasms; Vincristine

We report on a primary mediastinal large B-cell lymphoma with aberrant expression of beta-human chorionic gonadotropin (beta-hCG). The patient, a 33-year-old man, had cough, dyspnea, fever, superior vena cava syndrome, and a mediastinal bulky tumor. A biopsy showed that the latter was characterized by large cells, sclerosis, and compartmentalization. The neoplastic elements expressed CD45, CD20, CD79a and, partially, CD30, whereas they were negative for CD3, epithelial membrane antigen and cytokeratins. Surprisingly, they displayed a clear-cut positivity for beta-hCG. The remaining oncofetal markers applied (PLAP and alpha1-fetoprotein) were negative. Electron microscopy demonstrated the presence of numerous nuclear pockets and the lack of intercellular junctions. DNA analysis by polymerase chain reaction showed clonal rearrangement of Ig heavy-chain genes. The patient responded promptly to the administration of MACOP-B. To the best of our knowledge, this is the first example of B-cell lymphoma showing positivity for beta-hCG; a similar aberrant expression was previously observed only in three Japanese patients with human T-cell lymphotropic virus type I+ adult T-cell lymphoma/leukemia. Because primary mediastinal large B-cell lymphoma has in the past been frequently confused with germ cell tumors, pathologists should be aware of possible beta-hCG expression by lymphomatous cells to avoid the risk of misdiagnosis.

Topics: Adult; Antigens, CD; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cell Nucleus; Chorionic Gonadotropin, beta Subunit, Human; Cyclophosphamide; DNA, Neoplasm; Doxorubicin; Gap Junctions; Humans; Immunoglobulin Heavy Chains; Immunohistochemistry; Leucovorin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Mediastinal Neoplasms; Methotrexate; Polymerase Chain Reaction; Prednisone; Sequence Analysis, DNA; Tomography, X-Ray Computed; Treatment Outcome; Vincristine

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Mandibular Neoplasms; Methotrexate; Middle Aged; Prednisone; Remission Induction; Transplantation, Autologous

To evaluate clinical outcome of patients with testicular diffuse large-cell lymphoma treated with conventional-dose systemic chemotherapy.. This study is a retrospective analysis of adult patients with testicular diffuse large-cell lymphoma who were treated with a doxorubicin-based chemotherapy regimen at our institution, the Istituto Nazionale Tumori of Milan. Twenty-nine assessable patients, with a median age of 61 years, were identified. Sixteen patients had limited stage (Ann Arbor stage I/II) disease, whereas 13 patients had a testicular mass and distant organ involvement (Ann Arbor stage IV). Patients were retrospectively classified according to the International Prognostic Index.. After a median follow-up of 82 months, 22 patients presented disease progression and 22 patients had died. Actuarial median time to treatment failure and overall survival were 44 and 41 months for patients with limited stage and 9 and 16 months for patients with advanced stage, respectively. Eight patients failed initial treatment, and 14 patients relapsed from clinical remission after a median disease-free time of 17 months (range, 6 to 98 months). Median survival time after progression of lymphoma was 5 months (range, 0 to 22 months). In nine (41%) of the 22 failing patients, the initial site of relapse was either the CNS or the contralateral testis; the remaining patients experienced relapse in multiple extranodal sites.. Poor prognosis of patients with diffuse large-cell lymphoma calls for more effective treatment strategies, such as high-dose chemotherapy programs for younger patients or specifically designed chemotherapy regimens for patients not suitable for high-dose treatment, with the purpose to provide control of both systemic disease and disease of the CNS and contralateral testis. The potential benefit of contralateral testicular irradiation has to be taken into account in the treatment planning.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Disease Progression; Doxorubicin; Etoposide; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Neoplasm Staging; Prednisone; Prognosis; Prospective Studies; Recurrence; Retrospective Studies; Salvage Therapy; Testicular Neoplasms; Treatment Outcome; Vincristine

In our previous study with MACOPB, we identified a high-risk group of patients with a poor 3-year survival rate of 29%. These patients were defined as having at diagnosis advanced-stage disease with high tumor burden (TB) and elevated lactate dehydrogenase (LDH) level or bone marrow (BM) involvement. A novel therapeutic scheme was investigated to improve the outcome of these patients.. Fifty patients with high-risk diffuse large-cell lymphoma (DLCL) were enrolled. The therapeutic scheme includes three phases: induction with 8 weeks of MACOPB; intensification with a 3-day course of mitoxantrone 8 mg/m2 plus high-dose cytarabine (HDARA-C) 2 g/m2 every 12 hours plus dexamethasone 4 mg/m2 every 12 hours (MAD protocol) and granulocyte colony-stimulating factor (G-CSF) 5 microg/kg on days 4 to 17 to harvest peripheral-blood progenitor cells (PBPC); consolidation with carmustine (BCNU), etoposide, ARA-C, and melphalan (BEAM) regimen; plus autologous stem-cell transplantation (ASCT) with PBPC, marrow, or both.. Thirty-six patients (72%) achieved a complete response (CR), 11 (22%) showed no response (NR), and three (6%) died of toxicity. Among the 22 PRs or NRs after the induction phase, 56% of patients achieved a CR with subsequent intensified therapy. With a median follow-up duration of 32 months, the overall survival and failure-free survival rates were 56% and 50%, respectively. The disease-free survival rate is 69% at 32 months. Leukapheresis after MAD and G-CSF yielded a median of 32 x 10(6)/kg CD34+ cells and 80 x 10(4)/kg granulocyte-macrophage colony-forming units (CFU-GM). Thirty-nine patients were autografted and 11 did not undergo ASCT: six because of disease progression, four due to toxicity, and one because of patient refusal. The median times to achieve engrafment were 11 days (range, 7 to 19) to a neutrophil count greater than 0.5 x 10(9)/L and 12 days (range, 8 to 60) to a platelet count greater than 50 x 10(9)/L.. This sequential scheme with intensified and high-dose chemotherapy with ASCT is feasible with moderate toxicity and may improve the outcome in high-risk DLCL.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Carmustine; Cyclophosphamide; Cytarabine; Dexamethasone; Disease-Free Survival; Doxorubicin; Etoposide; Feasibility Studies; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Leucovorin; Leukapheresis; Lymphoma, Large B-Cell, Diffuse; Male; Melphalan; Methotrexate; Middle Aged; Mitoxantrone; Pilot Projects; Prednisone; Risk; Survival Analysis; Transplantation, Autologous; Treatment Outcome; Vincristine

To examine the clinical course of patients who experienced a late relapse after initial curative chemotherapy for advanced-stage diffuse large-cell lymphoma.. Between April 1981 and June 1986, 127 patients with de novo advanced-stage diffuse large-cell lymphoma were treated with a 12-week chemotherapy program (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B]). The overall survival rate at 10 years is 52%. One hundred six patients (83%) entered a complete remission (CR) and 43 of them relapsed. With a median follow-up duration of 146 months, 26 patients relapsed early and 17 relapsed late, ie, after a continuous CR (cCR) of greater than 24 months. All late relapses occurred in patients with B-cell lymphoma.. After 24 months from diagnosis, the rate of late relapse averaged 2.2% per year and reached a projected 22% actuarial risk of late relapse after 10 years. The median time to late relapse was 69 months (range, 38 to 141). Ten patients relapsed with aggressive histologic subtypes and were treated with curative intent using anthracycline-based chemotherapy. Four remain in second CR, one is alive with disease, and five died of disease or while on treatment. The 6-year overall survival rate from the time of relapse (SFR) for these 10 patients is 42%. Six patients relapsed with low-grade follicular lymphoma. These patients received various treatments intended to control, but not necessarily cure disease. One is in second CR, one is alive with disease, and four died of disease or while on treatment. The 6-year overall SFR rate for these six patients is 40%. bcl-2 translocation and Bcl-2 protein expression at diagnosis did not predict for the type of late relapse. One patient did not undergo repeat biopsy at relapse and died 9 months later despite aggressive therapy.. Curative therapy should be attempted in patients who relapse late with aggressive-histology lymphoma and those who relapse with follicular histology may benefit from palliative treatment. The behavior of late-relapse lymphoma is similar to de novo lymphoma, with outcome dictated by the histologic subtype at relapse.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Neoplasm Staging; Prednisone; Prognosis; Proto-Oncogene Proteins c-bcl-2; Recurrence; Salvage Therapy; Survival Rate; Time Factors; Vincristine

In two consecutive and unselected cohorts of diffuse large cell lymphoma (DLCL) patients with advanced stage disease (IIB or bulk or more) and aged < 60 years, we compared a standard (MACOP-B for 12 weeks, 60 patients) versus a high-dose chemotherapy programme (8 weeks of MACOP-B plus one or two cycles of intensification with mitoxanthrone, dexamethasone, high-dose Ara-C, and finally BEAM chemotherapy with autologous haemopoietic progenitor cell transplantation, 61 patients). 41 patients (68%) in the standard group and 51 (84%) in the high-dose chemotherapy group, achieved a complete remission (CR) or an uncertain complete remission (CRu) (P = 0.0491). With a median follow-up time of 28 months for the high-dose group and 63.5 months for the standard group, the actuarial estimate of event-free survival (EFS) at 2 years demonstrates a significant benefit (70% v 50%, P = 0.03) for patients treated with the intensive regimen. The analysis of subgroups of patients showed that only high-risk patients (two or three risk factors) benefitted from the high-dose chemotherapy programme. Nevertheless, the overall survival does not show a significant difference between the two treatment modalities. The treatment-related morbidity was similar and the mortality rate was 8% in the standard (MACOP-B) group and 3% in the high-dose chemotherapy programme. In conclusion, our results show that high-dose chemotherapy and autologous stem cell transplantation is a safe procedure which should be considered for the front-line treatment of non-Hodgkin lymphoma patients with poor prognostic features.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carmustine; Cyclophosphamide; Cytarabine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Melphalan; Methotrexate; Middle Aged; Prednisone; Survival Rate; Treatment Outcome; Vincristine

To define both the natural history of and prognostic factors affecting outcome post relapse from a complete response in advanced stage diffuse large-cell lymphoma.. A total of 468 patients aged 17-74 years received the 12-week duration chemotherapy regimens MACOP-B, VACOP-B and ACOP-12 between 1 April 1981 and 31 December 1995 for advanced stage diffuse large, mixed or immunoblastic lymphoma. Of these 402 entered a complete remission, 97 (24%) of whom subsequently relapsed. Initial staging data, follow-up, and relapse information were analyzed to define the natural history of relapse and also subjected to univariate and multivariate correlation with overall (OS) and failure free survival (FFS).. Eleven percent of the relapses were low grade. All other relapses were of intermediate grade with 75% occurring within the first two years, the remainder up until the eleventh year. Median and five-year OS from the time of relapse for intermediate grade relapse were 12 months and 20%; for FFS they were eight months and 18% respectively. Adverse independent factors, for both OS and FFS were: less than one year to relapse, decreasing performance status at relapse, and more than three nodal sites at relapse.. Low-grade relapse is not uncommon in patients who initially presented with diffuse large cell lymphoma. As the management of low- and intermediate grade disease is so different biopsy proof of the nature of the relapse is of value. The prognostic factors identified need to be taken into consideration when analyzing results from trials of secondary treatment so as to avoid erroneous conclusions about comparative treatment efficacy.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Multivariate Analysis; Prednisone; Prognosis; Recurrence; Retrospective Studies; Vincristine

A case of NHL which has been in long-term remission following vigorous treatment for CNS relapse with intrathecal administration of Ara-C and focal irradiation to the brain is presented. The patient was a 61-year-old man, who was successfully treated with CHOP followed by MACOP-B for diffuse large cell NHL in 1988. Five months later he was admitted to our hospital because of loss of visual acquity and numbness in the right upper and lower extremities. The presence of lymphoma cells in CSF, abnormal shadow in the left frontal lobe on a cranial CT scan and MRI scan, and positive Ga scintigraphy yielded a diagnosis of CNS relapse of NHL. Twenty one whole brain and additional 1.0Gy to the left frontal lobe of irradiation were performed. Eight days later the left tumor disappeared. Neurological remission was obtained and has continued until now.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Brain Neoplasms; Cyclophosphamide; Doxorubicin; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Prednisone; Remission Induction; Vincristine

Spinal cord compression as first presentation of non-Hodgkin's lymphoma (NHL) is an uncommon event. Diagnosis of NHL usually is performed on a laminectomy specimen. Spinal cord compression has been reported in 5% of patients with solid tumors. Although this clinical picture has been considered as very unusual among NHL patients, some series regarding descompresive laminectomy indicate that NHL was the underlying cause in 15% of these cases. We report two cases of patients with NHL who presented paraparesia secondary to spinal cord compression due to lymphomatous mass in the epidural region which was showed by magnetic resonance imaging. The emergency laminectomy and treatment with chemotherapy allowed the clinical recuperation of both patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Epidural Space; Etoposide; Female; Humans; Laminectomy; Leucovorin; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Mechlorethamine; Methotrexate; Middle Aged; Paresis; Paresthesia; Prednisone; Procarbazine; Soft Tissue Neoplasms; Spinal Cord Compression; Spinal Neoplasms; Thoracic Neoplasms; Thoracic Vertebrae; Urinary Retention; Vincristine

Adriamycin containing combination chemotherapy (ACCC) is usually delivered to patients with stages III, IV diffuse large cell (DLCL) non-Hodgkin's lymphoma (NHL). Although this mode of therapy is also commonly used in other intermediate grade lymphomas, it's role in the latter subset of patients is not well defined. In a retrospective analysis we evaluated and compared the outcome of previously untreated DLCL and non-DLCL intermediate grade lymphoma patients who received as initial therapy, "first generation" ACCC. No differences in response and relapse rates between these subgroups were observed. The trend towards the survival advantage observed for the non-DLCL patients, is probably due to a lower mortality over 5-8 years, for complete responders.

Topics: Actuarial Analysis; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Cyclophosphamide; Dexamethasone; Doxorubicin; Etoposide; Follow-Up Studies; Humans; Leucovorin; Lomustine; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Melphalan; Methotrexate; Middle Aged; Phosphoramide Mustards; Prednisolone; Prednisone; Prognosis; Retrospective Studies; Survival Analysis; Time Factors; Treatment Outcome; Vincristine

From October 1984 to December 1989, 59 patients with aggressive non-Hodgkin's lymphomas (diffuse mixed, diffuse large cell, and immunoblastic) were treated with MACOP-B. All patients were previously untreated and most of them had advanced disease. Complete response (CR) was observed in 66%. Actuarial overall survival, failure-free survival (FFS), and relapse-free survival at 8 years were 54%, 52%, and 81%, respectively, with a median follow-up of 76 months (range: 28-92 months). The presence of B symptoms influenced significantly the CR rate, while FFS was affected by B symptoms, bone marrow involvement, and number of extranodal sites. Toxicity was high, with mucositis grade 2 or 3 occurring in 70%, leukopenia grades 3 or 4 in 80%, and death in 11.8% of the patients. MACOP-B was active in the treatment of aggressive non-Hodgkin's lymphomas, mainly in patients with few poor-prognosis factors, but other less toxic regimens would be more appropriate for this population. For poor-prognosis patients, new therapeutic modalities are necessary.

Topics: Actuarial Analysis; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Brazil; Cyclophosphamide; Doxorubicin; Female; Follow-Up Studies; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prednisone; Prognosis; Prospective Studies; Remission Induction; Socioeconomic Factors; Survival Rate; Vincristine

Between 1981 and 1986, 126 patients with advanced stage, large cell lymphoma were treated with MACOP-B chemotherapy. Their six-year failure-free and overall survival is 52% and 62% respectively. Eighty-eight patients aged 60 or less had an excellent six year overall survival of 68%. The outcome for various subsets of patients is analysed according to the number of adverse prognostic factors including age, stage, lactic dehydrogenase level and number of extra nodal sites.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Methotrexate; Middle Aged; Prednisone; Prognosis; Survival Rate; Vincristine

The efficacy and toxicity of the MA-COP-B regimen were assessed after outstanding results were reported in diffuse large cell lymphoma (DLCL) by the Vancouver group. The results are reported according to several proposed prognostic indices, including the recent International Prognostic Factors (IPF) Project.. Forty-seven patients with untreated DLCL received MACOP-B chemotherapy. Thirty patients, most of whom had bulky disease, also received consolidative radiation therapy (RT). Patient characteristics include median age of 42 years, Stage III/IV (57%), bulky or symptomatic Stage II disease (43%), elevated lactic dehydrogenase (81%) and at least one extranodal site (72%).. At a median follow-up of 3.3 years, overall survival was 57% and freedom from progression (FFP) was 52%. The 3-year FFP data were related to tumor extent: 74% for limited stage versus 38% for extensive disease. These data correlated well with four prognostic indices reported in the literature. The IPF index accurately identified low-, intermediate-, and high-risk subgroups.. Patients with limited or low-risk DLCL have an excellent prognosis with MACOP-B +/- RT. These results do not support the use of consolidative high-dose therapy and bone marrow transplantation in patients with limited disease, even if bulky or accompanied by an elevated lactic dehydrogenase. Compared to historical CHOP data, MACOP-B +/- RT does not appear to improve outcome for those patients with poor prognostic features, most of whom will fail. The IPF index is a simple, accurate method of distinguishing high-risk patients who require new therapeutic initiatives.

Topics: Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Follow-Up Studies; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Prognosis; Remission Induction; Risk Factors; Survival Rate; Vincristine

Two cases of non-Hodgkin's lymphoma suffered from acute respiratory failure. Both patients were treated with MACOP-B therapy, and received recombinant granulocyte-colony stimulating factor (rG-CSF) during the myelosuppression. They had fever and severe hypoxemia several days after 11 and 12-week's treatment, respectively. The chest X-ray films revealed diffuse fine granular shadows in bilateral lung fields. The number of white blood cells had rapidly increased when the shadows appeared. These cases suggested the possibility that rG-CSF, or the rapid increase of white blood cells, might induce interstitial pneumonia.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Leukocytosis; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Prednisone; Pulmonary Fibrosis; Recombinant Proteins; Vincristine

Between 1982 and 1990, we treated patients with poor prognosis non-Hodgkin's lymphoma (NHL) with inpatient, dose-intensive multidrug chemotherapy. Dose intensity was approximately 2.6 times that of the standard CHOP regimen. All patients had intermediate or high grade NHL, as well as one or more clinical features predictive of poor prognosis. Initial results were previously reported in a group of 56 patients, and in a subgroup of 20 patients with small noncleaved cell lymphoma. In this report, we present long-term followup of the patients previously reported. Median follow up is now 75 months (range 48-122 months). Since our initial reports, the survival curves have remained essentially unchanged, with an actuarial 5 year survival of 48% for the entire group and 60% for the patients with small noncleaved cell lymphoma. Disease-free survival is 42% for patients in Shipp's category 3. Three late relapses occurred, all > 36 months after treatment. No late toxicities or second malignancies have been observed. Intensive, short duration therapy is feasible and effective, and may provide particular advantage to patients with small noncleaved cell histology or other poor prognostic features. Exploration of the importance of dose intensity in lymphoma treatment should continue; comparison of this regimen with standard CHOP is indicated.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Etoposide; Female; Follow-Up Studies; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Prednisone; Prognosis; Survival Analysis; Vincristine

A 33-year-old Japanese woman visited our hospital with progressive dyspnea. A chest roentgenogram and a chest computed tomogram revealed a mediastinal tumor and pericardial effusion. Ultrasound cardiography revealed the existence of cardiac tamponade. She was successfully treated with emergency pericardial drainage, thoracocentesis and chemotherapy. The histological diagnosis of diffuse large B cell lymphoma was established with the tumor specimen obtained by transcutaneous fine needle aspiration biopsy and through immunohistochemical analysis. This is a rare case of primary mediastinal diffuse large cell lymphoma with initial presentation of a symptom related to pericardial effusion.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cardiac Tamponade; Cyclophosphamide; Doxorubicin; Female; Humans; Immunohistochemistry; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Mediastinal Neoplasms; Methotrexate; Pericardial Effusion; Prednisone; Vincristine

Discordant lymphomas, in particular nodal large-cell lymphomas with marrow small-cell lymphoma, were discovered recently, and the prognosis of patients with such disease has been discussed. The small cells were reported to be small lymphocytic or small cleaved lymphoma cells. We have detected, by kappa-lambda imaging (KLI) with delta-curves, using a flow cytometer, small lymphoma cells in the peripheral blood (PB) and bone marrow (BM) of 41 untreated patients with various B-cell lymphomas expressing surface Ig (sIg+BCL), and evaluated their clinical and prognostic significance. Small cells were found in approximately 90% (37 of 41) of sIg+BCL patients when either PB or BM was analyzed and, overall, the presence of small cells correlated well with the disease activity. However, in some patients, a few cells remained in the PB (16%) or BM (27%) even when they were in remission, whereas in others, the cells were presented in the PB or BM several months before relapse. These results suggest that the detection of small cells in PB or BM by KLI may be helpful for screening and monitoring patients with sIg+BCL. When the patients were subdivided into three groups (normal, low, and high amplitude), according to the abnormal grade criteria of the delta-curves, which were based on the results of both PB-KLI and BM-KLI, the survival of the high-amplitude group tended to be shorter than that of the normal group (P = .068), which was particularly marked when the follow-up period exceeded 2 years. Moreover, as the group grading worsened (normal less than low less than high), the complete response rates deteriorated (100%, 71%, and 60%, respectively) and the respective relapse rates after complete remission increased (17%, 40%, and 67%). Thus, the determination of the proportion of small lymphoma cells in PB and BM by KLI may be useful for predicting the prognoses of patients with sIg+BCL.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow; Cyclophosphamide; Doxorubicin; Flow Cytometry; Humans; Leucovorin; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocytes; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Methotrexate; Neoplasm Recurrence, Local; Prednisone; Prognosis; Remission Induction; Vincristine

One hundred twenty-six patients with diffuse large-cell lymphoma were treated with methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) between April 1981 and June 1986. Univariate and multivariate analyses were performed using overall survival as of September 1989 as the end point. Four independent negative predictors of survival were identified: presence of B symptoms; more than two involved lymph node sites; more than one extranodal site (variables related to tumor burden), and age older than 60, a variable related to the patient's ability to tolerate treatment. Each variable contributed the same relative risk of dying and, accordingly, this simple predictive formula was developed empirically: (4-N) x 30 = the approximate percentage of chance of survival at 5 years. "N" is the number of predictive variables present. The same four predictors were also found to be significant by multivariate analysis when only those patients achieving a complete response were analyzed.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Humans; L-Lactate Dehydrogenase; Leucovorin; Lymphatic Metastasis; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Multivariate Analysis; Neoplasm Staging; Prednisone; Prognosis; Retrospective Studies; Survival Rate; Vincristine

Between 1981 and 1986, 126 patients with diffuse large cell lymphoma were treated with MACOP-B (methotrexate/doxorubicin/cyclophosphamide/vincristine/prednisone/bleomy cin). All had advanced-stage lymphoma (Ann Arbor stage III or IV or stage I or II if the tumor mass was greater than 10 cm or B symptoms were present). The complete response (CR) rate was 84% and the toxic death rate was 6%. Actuarial overall survival at 3 years was 67% and at 8 years 62%; the failure-free survival at 8 years was 52%. The follow-up for MACOP-B is 39 to 106 months (median 76) for living patients. A multivariate prognostic factor analysis for this group of patients identified age greater than 60 years. B symptoms, more than one extranodal site of disease, and more than three nodal sites of disease as the four significant prognostic variables. From June 1986, 108 patients were enrolled on a modification of MACOP-B called VACOP-B (etoposide/doxorubicin/cyclophosphamide/vincristine/prednisone/bleomycin ). Their CR rate was 81%, and the toxic death rate was lower, at 3%. The 60% overall survival at 3 years is not statistically significantly different from that of MACOP-B. The incidence of moderate or severe mucositis and Cushingoid changes was much lower with VACOP-B. The MOPP/ABV (mechlorethamine/vincristine/procarbazine/prednisone- doxorubicin/bleomycin/vinblastine) hybrid chemotherapy regimen for advanced-stage Hodgkin's disease was standard therapy from April 1981 to June 1988 for untreated patients aged 16 to 65. Advanced stage was defined as stages IIB, IIIB, III2A, IVA, IVB, or stages IIA or IIIA with greater than four splenic nodules or a mediastinal mass greater than one third of the transthoracic diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Actuarial Analysis; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Evaluation; Etoposide; Female; Hodgkin Disease; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Mechlorethamine; Methotrexate; Middle Aged; Mouth Mucosa; Prednisone; Procarbazine; Prognosis; Remission Induction; Stomatitis; Survival Rate; Vinblastine; Vincristine

To investigate the results of the treatment of large-cell non-Hodgkin's lymphomas (LCNHL) with the MACOP-B chemotherapy protocol.. 20 patients with the following inclusion criteria were treated: LCNHL with a definite majority of large lymphoid cells and absence of previous therapy, HIV infection or severe underlying diseases.. Three patients died during therapy and 15 (75%) achieved a complete remission. Actuarial survival after 36 months (0.66) was significantly better (p = 0.05) than that of a comparable historical series of LCNHL treated with CHOP (0.28). Age, stages III-IV, B symptoms, large lymphatic mass (LLM) and bone marrow infiltration did not negatively affect survival. The toxicity of the MACOP-B protocol was high: mucositis (65%), cytopenia (55%), neuropathy (40%), complications of steroid therapy (15%), and mortality directly related with therapy in 15%. Residual masses were found after therapy in 7% (70%) with BD, which were localized in lymphoid areas or in parenchyma (spleen and kidney). Surgical exploration showed that the residual masses were not tumoral in three cases, and in another three magnetic resonance suggested inactive disease.. The MACOP-B protocol is highly effective for the treatment of LCNHL. The essential prognostic factor for survival in these NHL appears to be the cell composition with a great majority of large cells.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Evaluation; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Methotrexate; Prednisone; Remission Induction; Time Factors; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Doxorubicin; Fluorouracil; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Vincristine

One hundred six eligible patients with advanced intermediate- or high-grade malignant lymphoma were treated with methotrexate with leucovorin rescue, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) in a Southwest Oncology Group phase II trial. Patients were stratified by estimated bone marrow reserve, and impaired marrow reserve patients received reduced doses of cyclophosphamide and doxorubicin. The complete remission rate for normal marrow reserve patients was 65%, while the complete remission rate for impaired marrow reserve patients was 29%. With a median follow-up period of 41 months, 64% of complete responders in the normal marrow group are disease-free 3 years after their response. Three-year survival is 61% in the normal marrow reserve group and is 29% in the impaired marrow reserve group. Eighty-seven percent of treatment courses were given in accordance with protocol dosing and schedule. For doxorubicin, relative dose intensities were 0.75 and 0.61 (normal and impaired marrow reserve arms, respectively), for cyclophosphamide, 0.76 and 0.61, and for methotrexate, 0.55 and 0.45. Serum lactic dehydrogenase (LDH) level was the only pretreatment characteristic found to have a significant effect on overall survival. Severe or greater toxicity occurred in 97% and 89% of the normal and impaired marrow reserve groups, respectively, with granulocytopenia the principal toxicity. Treatment-related fatalities occurred in 8% of patients. m-BACOD is an effective but toxic treatment program for intermediate- and high-grade malignant lymphomas.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; L-Lactate Dehydrogenase; Leucovorin; Leukocyte Count; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Neoplasm Staging; Survival Analysis; Vincristine

The authors recently reported the antigenic phenotypes of three cases of so-called "malignant angioendotheliomatosis" and suggested that angiotropic large cell lymphoma (ALCL) is a more appropriate designation for this disease. The authors now report an additional seven cases of ALCL with unique clinical presentations. One patient presented with prostate enlargement, the second with lytic bone lesions and thickened nasal sinus mucosa, the third had diffuse myalgia, the fourth had dyspnea and pulmonary infiltrates, the fifth had gangrene of the lower extremities, total-body skin involvement, and pancytopenia, the sixth had a lesion of the foreskin mimicking squamous cell carcinoma, and the seventh had a mediastinal mass. In all cases histologic features were characteristic of ALCL with, in two cases, extravascular spread into soft tissue. Immunohistologic studies showed a B-cell phenotype in five cases and a T-cell phenotype in one case. Two patients received combination chemotherapy using established treatment protocol for large cell lymphoma, and remain in complete clinical remission and two patients are responding clinically to combination chemotherapy. Two patients died shortly after receiving combination chemotherapy. One patient has only recently been diagnosed as having ALCL and no long-term follow-up is available. These data indicate that, although ALCL affects predominantly the central nervous system and skin, unusual clinical presentations may occur, and patients with ALCL may respond to combination chemotherapy for large cell lymphoma.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Immunohistochemistry; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Prednisone; Procarbazine; Vincristine

Identification of prognostic groups among patients with diffuse large-cell (histiocytic) lymphoma (DHL) would help to select specific therapy for individual patients and allow comparisons among combination chemotherapy clinical trials. The Ann Arbor staging system is of limited value in predicting outcome in diffuse histiocytic lymphoma. Prognostic factors have been examined by various groups without a consensus of reliable prognostic indicators. This study was undertaken to examine the validity of a predictive model for response to treatment and survival in DHL. Eighty-six patients with the diagnosis of DHL treated with combination chemotherapy between the years 1976 and 1982 were examined for prognostic variables influencing response to treatment and survival. The variables examined included: age, sex, presence or absence of systemic symptoms, serum lactic dehydrogenase (LDH), sites of disease involvement, bulk of disease, prior therapy, stage of disease, according to the Ann Arbor classification, and pathological criteria, according to the Lukes Collins classification. Factors achieving a p-value in the 0 to 0.05 range with univariate analysis for predicting response were age and systemic symptoms. Factors significant for overall survival were age and bone marrow involvement. These factors have been found to influence survival in previous studies, but there has not been a consistency regarding the importance of these factors. Large numbers of patients must be examined for various factors in order to allow identification of prognostic groups among patients with DHL.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow; Cyclophosphamide; Cytarabine; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Prednisone; Procarbazine; Prognosis; Vincristine

Between April 1981 and May 1984, 61 patients with advanced diffuse large-cell lymphoma completed treatment with MACOP-B (methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin), an innovative pilot chemotherapy program emphasizing weekly treatment, antibiotic prophylaxis, daily corticosteroid treatments, and brief duration (12 weeks). Fifty-one patients (84%) achieved a complete response and 10 patients (16%) had a partial response. Over a median follow-up after treatment of 23 months, the actuarial overall survival for the entire group has been 76%; for complete responders the relapse-free survival has been 90%. Toxicity was modest with one treatment-related death and seven episodes of serious infection. The most frequent toxicity was mucositis. Thus, MACOP-B is an effective treatment for large-cell lymphoma that can be delivered in 12 weeks with an acceptable incidence of toxicity. This regimen can achieve results similar and possibly superior to those of other presently used regimens of longer duration.

Topics: Actuarial Analysis; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Arachnoid; Bleomycin; Bone Marrow; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Humans; Inflammation; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Meningeal Neoplasms; Methotrexate; Middle Aged; Mucous Membrane; Neoplasm Staging; Pia Mater; Prednisone; Vincristine

From January 1970 to March 1981, localized diffuse histiocytic lymphoma (DHL) was identified in 31 patients by exploratory laparotomy and splenectomy (pathologic stage I, 17 patients; pathologic stage II, 14 patients) at the University of Chicago. The median follow-up time was 72 months. All patients were previously untreated and received radiation therapy as their primary treatment modality. Chemotherapy was administered only at the time of relapse. All but two patients achieved a complete remission (CR) with radiation therapy. The actuarial disease-free survival for patients with stage I disease is 94% at 5 years and 72% at 10 years. For stage II disease, the disease-free survival is 56% at 5 years and 31% at 10 years. The difference in the disease-free survival between stage I and II is statistically significant (P = .02). The survival at 10 years is 70% for stage I disease and 46% for stage II disease. Five patients had documented relapses (four had stage II disease). Only two of those who relapsed achieved a second CR with salvage chemotherapy. Our data show an excellent outcome in patients with pathologic stage I disease, indicating that a high percentage of these cases can be cured with radiotherapy alone. Patients with clinical stage II disease might be served better with chemotherapy.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Female; Humans; Leucovorin; Lymphatic Metastasis; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Neoplasm Staging; Prognosis; Radiation Injuries; Vincristine

A new combination chemotherapy program (M-BACOD) was administered to 101 patients with advanced diffuse histiocytic and diffuse undifferentiated lymphoma (DHL and DUL). High dose methotrexate (M) 3 g/m2 with leucovorin factor rescue was given on day 14 between cycles of bleomycin (B), adriamycin (A), cyclophosphamide (C), oncovin (O), and dexamethasone (D) administered every 3 weeks for 10 cycles. The complete remission rate (CR) was 72% in all 101 patients or 77% in 95 evaluable patients. The median follow-up is 3 yr 2 mo with one-third of CR patients followed beyond 4 yr. Twenty-six percent of CR patients have relapsed with a projected 5-yr survival rate of 80% (5-yr disease-free rate 65%). The overall survival of all 101 study patients reaches a plateau at 59% projected out to 5 yr. Patients with prior therapy had a significantly lower CR rate than those without prior treatment (p = 0.001); however, no other unfavorable prognostic characteristics could be identified. Relapse in the central nervous system CNS occurred in only 5.4% of CR patients. M-BACOD results in prolonged survival and possible cure in a high proportion of all patients with DHL and DUL.

Topics: Actuarial Analysis; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow; Cyclophosphamide; Dexamethasone; Dose-Response Relationship, Drug; Doxorubicin; Female; Follow-Up Studies; Humans; Leucovorin; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Male; Meningeal Neoplasms; Methotrexate; Middle Aged; Prognosis; Vincristine

Sixteen patients with resistant non-Hodgkin's lymphoma were treated with continuous infusions of vincristine (1-2 mg/m2 daily X 2 days) and bleomycin (0.25 mg/kg bolus dose, then 0.25 mg/kg/daily X 5 days). Responding patients received high dose methotrexate (1500 mg/m2) with citrovorum rescue on days 15, 22, 29, 36. Treatment cycles were repeated every six weeks in responding patients. The response frequency was 50% (three complete and five partial responses). Median response duration was 29 weeks. Major toxicity included stomatitis (63%) and leukopenia (44%). One episode each of possible hypersensitivity pneumonitis and paralytic ileus occurred. Continuous infusions of vincristine and bleomycin should be studied further in less critically ill patients.

Topics: Adult; Aged; Bleomycin; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Humans; Infusions, Parenteral; Leucovorin; Leukopenia; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Stomatitis; Time Factors; Vincristine

The Lukes and Collins classification was applied to 47 patients who received COMLA (cyclophosphamide, vincristine, methotrexate, leucovorin, and cytarabine) as initial treatment for diffuse histiocytic lymphoma (DHL). Pathologic staging was complete in 39 of 47 patients; two patients had stage IIE disease, 17 had stage III, and 28 had stage IV. Complete remission, which was documented by extensive clinical restaging, was achieved in 25 (64%) of 39 patients with morphologic B-cell lymphomas and in only three of eight patients with non-B-cell lymphomas. The medial duration of complete remission is significantly longer in patients with B-cell lymphomas than in those with non-B-cell lymphomas (45 + versus 13 months, P less than 0.01). Among patients with DHL, median survival is significantly longer for those with B-cell lymphomas than for those with lymphoma of T-cell or in determinate origin (60 + versus 6 months, P less than 0.01). While DHL is regarded as a curable disease, patients not achieving complete remission are rarely salvaged; median survival for these patients was 10 months. The Lukes and Collins classification allows us to identify patients with DHL in whom newer therapies are needed for initial treatment. Further study may enable us to identify additional unfavorable subsets in the B-cell category.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Female; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Prognosis; Vincristine

Topics: Antineoplastic Agents; Cyclophosphamide; Cytarabine; Doxorubicin; Humans; Leucovorin; Leukopenia; Lymphoma, Large B-Cell, Diffuse; Methotrexate; Prednisone; Procarbazine; Radiotherapy, High-Energy; Thrombocytopenia; Vincristine

A program of combination sequential chemotherapy using cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) was administered to 42 previously untreated patients with advanced diffuse histiocytic lymphoma. Twenty-three patients achieved a complete remission as determined by strict clinical restaging criteria. The observed median duration of survival for the complete responders is longer than 33 months. Eight patients achieved a partial response, with a median survival longer than 21 months. Eleven patients showed no response, with a median survival of 5 months. Toxicity was acceptable. None of the responders have shown central nervous system relapse. There was no difference in response rates between patients with stage III or IV lymphoma or between asymptomatic or symptomatic patients. The COMLA program produces a high rate of complete and durable remissions and should be considered as an initial form of management of patients with advanced diffuse histiocytic lymphoma.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Female; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Prospective Studies; Tennessee; Vincristine

Topics: Antineoplastic Agents; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Methotrexate; Vincristine

Three patients, in whom tumour overkill by cytotoxic treatment, including high dose methotrexate with folinic acid rescue, resulted in the 'phosphate shower syndrome' (hyper-uricaemia, hyperkalaemia and hyperphosphataemia with hypocalcaemia and tetany, with metabolic acidosis and acute renal impairment) are described. Severe methotrexate toxicity occurred in two of these patients. High dose methotrexate would appear contra-indicated in situations where massive tumour lysis is possible.

Topics: Adolescent; Adult; Calcium; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Phosphates; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Topics: Adult; Aged; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Female; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Prednisone; Remission, Spontaneous; Vincristine

Topics: Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Methotrexate; Vincristine

Seven adult patients with advanced lymphoma, resistant to vincristine, prednisone, alkylating agents and Adriamycin were treated with "high dose" methotrexate and citrovorum factor rescue. Therapy consisted of 4 to 6-hour infusions of methotrexate (5--100 mg/kg) every 1 to 2 weeks with citrovorum rescue initiates 2 to 12 hours after termination of the infusion. Objective responses were obtained in three patients but these were short lived. Mucosal and hematologic toxicity occurred when repeat courses of therapy were administered. The results suggest that high dose methotrexate may be effective therapy in lymphoma, particularlly if citrovorum factor rescue is used early and in adequate dosage.

Topics: Adolescent; Aged; Antineoplastic Agents; Bone Marrow; Drug Resistance; Drug Therapy, Combination; Female; Humans; Infusions, Parenteral; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Remission, Spontaneous; Stomatitis; Time Factors

Seventeen patients with Stage III or IV reticulum cell sarcoma were treated with three cycles of a 5-drug regimen between February, 1969 and December, 1970. Of the 17 patients, 9 attained a complete remission and 6 had a parital remission; 2 were considered unevaluable. Recently, the original biopsies from these patients were reclassified according to the criteria of rappaport et al. The results were: diffuse histiocytic--8; nodular histiocytic--2; diffuse mixed--2; nodular mixed--3; diffuse lymphocytic poorly differentiated--1; nodular lymphocytic poorly differentiated--1. Of the 8 patients with diffuse histiocytic lymphoma 6 attained complete remission, 1 had a partial remission, and 1 was unevaluable. One of the 6 with complete remission relapsed at 7 months and died 2 months later. However, the other 5 are alive and in continued unmaintained remission for 55 to 65 months.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Female; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Remission, Spontaneous; Retrospective Studies; Time Factors; Vincristine

Topics: Adenocarcinoma; Administration, Oral; Aged; Carcinoma, Adenoid Cystic; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cystadenoma; Ear Neoplasms; Female; Head; Head and Neck Neoplasms; HeLa Cells; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Mouth Neoplasms; Osteosarcoma

Topics: Agranulocytosis; Antineoplastic Agents; Breast Neoplasms; Female; Hemangiosarcoma; Hodgkin Disease; Humans; Kidney Neoplasms; Leucovorin; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Lung Neoplasms; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Melanoma; Methotrexate; Osteosarcoma; Pancreatic Neoplasms; Radiography; Rectal Neoplasms; Rhabdomyosarcoma; Testicular Neoplasms; Thrombocytopenia

Topics: Adenocarcinoma; Arteries; Brain Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Catheterization; Chloramphenicol; Facial Neoplasms; Fever; Fluorouracil; Head and Neck Neoplasms; Humans; Infections; Infusions, Parenteral; Leucovorin; Liver Neoplasms; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Neoplasm Metastasis; Palliative Care; Penicillins; Stomach Neoplasms; Thoracic Neoplasms