levoleucovorin and Mediastinal-Neoplasms

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

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 aim of this subgroup analysis of the Mabthera International Trial Group study was to evaluate the impact of chemotherapy and rituximab in primary mediastinal B-cell lymphoma (PMBCL) in comparison to other diffuse large B-cell lymphoma (DLBCL).. Patients were randomly assigned to six cycles of CHOP-like regimens with or without rituximab.. Of 824 patients enrolled, 87 had PMBCL and 627 other types of DLBCL. Rituximab increased the rates of complete remission (unconfirmed) in both PMBCL (from 54% to 80%, P = 0.015) and DLBCL (from 72% to 87%, P < 0.001). In PMBCL, rituximab virtually eliminated progressive disease (PD) (2.5% versus 24%, P < 0.001), whereas without rituximab, PD was more frequent in PMBCL than in DLBCL (24% versus 10%, P = 0.010). With a median observation time of 34 months, 3-year event-free survival (EFS) was improved by rituximab for PMBCL (78% versus 52%, P = 0.012) and for DLBCL (81% versus 61%, P < 0.001). Overall survival benefit was similar for DLBCL (93% versus 85%, P < 0.001) and PMBCL (89% versus 78%, P = 0.158).. In young patients with PMBCL (age-adjusted International Prognostic Index 0-1), rituximab added to six cycles of CHOP-like chemotherapy increases response rate and EFS to the same extent as other DLBCL. The combination of rituximab with CHOP chemotherapy is an effective treatment in PMBCL with good prognosis features.

Topics: Adolescent; Adult; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Kaplan-Meier Estimate; Leucovorin; Lymphoma, B-Cell; Male; Mediastinal Neoplasms; Methotrexate; Middle Aged; Mitoxantrone; Multivariate Analysis; Prednisolone; Prednisone; Proportional Hazards Models; Prospective Studies; Rituximab; Treatment Outcome; Vincristine; Young Adult

To report the clinical findings and long-term results of front-line, third-generation MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin) chemotherapy and mediastinal involved-field radiotherapy (IFRT) in 85 consecutive, previously untreated patients with primary mediastinal large B cell lymphoma (PMLBCL) diagnosed and managed at a single institution.. Between 1991 and April 2004, 92 consecutive, untreated patients with PMLBCL were treated at our institution. The median age was 33 years (range, 15-61 years), 46 patients (50%) showed a mediastinal syndrome at onset; 52 patients (57%) showed a low/low-intermediate (0 to 1) and 40 patients (43%) an intermediate-high/high (2 to 3) International Prognostic Index (IPI) score. Eighty-five patients were treated with standard chemotherapy (MACOP-B), and 80 underwent mediastinal IFRT at a dose of 30-36 Gy.. After a MACOP-B regimen, the overall response rate was 87% and the partial response rate 9%. After chemotherapy, (67)Ga scintigraphy/positron emission tomography results were positive in 43 of 52 patients (83%), whereas after IFRT 11 of 52 patients (21%) remained positive (p < 0.0001). After a median follow-up of 81 months (range, 2-196 months), progression or relapse was observed in 15 of 84 patients (18%). The projected 5-year overall survival and progression-free survival rates were 87% and 81%, respectively. The 5-year overall survival and progression-free survival rates were better for patients with an IPI of 0 to 1 than for those with an IPI of 2 to 3 (96% vs. 73% [p = 0.002] and 90% vs. 67% [p = 0.007], respectively).. Combined-modality treatment with intensive chemotherapy plus mediastinal IFRT induces high response and lymphoma-free survival rates. Involved-field RT plays an important role in inducing negative results on (67)Ga scintigraphy/positron emission tomography in patients responsive to chemotherapy.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Humans; Italy; Leucovorin; Longitudinal Studies; Lymphoma, B-Cell; Mediastinal Neoplasms; Methotrexate; Middle Aged; Prednisone; Prevalence; Radiotherapy, Adjuvant; Survival Analysis; Survival Rate; Treatment Outcome; 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

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

To evaluate the clinical features of presentation and the response to two different third-generation regimens (F-MACHOP and MACOP-B) of primary mediastinal large B-cell lymphoma (MLBCL), a recently defined distinct clinicopathological entity of non-Hodgkin's lymphoma (NHL).. Thirty-seven consecutive patients with MLBCL, eight male and 29 female (F/M ratio 1:3.5) with a median age of 35 years, were enrolled in the present study. Thirty-five (94.5%) patients presented disease confined to thorax, with chest symptoms of a rapidly enlarging mass in the mediastinum in 70% and superior vena cava syndrome (SCVS) in 43% of these patients. The first 10 patients received F-MACHOP and the succeeding 27 patients MACOP-B chemotherapy, associated in 24 (88.8%) with involved field radiation therapy (IFRT). 67Gallium scan was routinely performed pre- and post-IFRT in 18 patients.. All 37 patients were assessable for response: 10 of 10 (100%) in the F-MACHOP and 26 of 27 (96.3%) in the MACOP-B group achieved overall responses (CR + PR). Three of 24 (12.5%) patients in PR after chemotherapy obtained CR after IFRT. Persistent Gallium avidity was observed in 16 patients after chemotherapy and in only four patients after IFRT. Thus far, four of the 10 F-MACHOP and two of the 26 MACOP-B responders have presented disease progression. The probability of progression-free survival (PFS) was 91% and 60% (P < 0.02) while overall survival (OS) was 93% and 70% (P = n.s.) at a mean follow-up of 27 and 52 months in the MACOP-B + IFRT and F-MACHOP groups, respectively.. MACOP-B + IFRT has proved to be a highly effective and less toxic therapeutic approach for primary MLBCL and appears to be superior to other third-generation chemotherapy regimens.

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

Treatment of both Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (HG-NHL) with bulky presentation at diagnosis frequently results in residual masses detected radiologically. Conventional diagnostic radiology and computed tomography (CT) are generally unable to detect the differences between tumor tissue and fibrosis. Gallium-67-citrate (67Ga) SPECT and magnetic resonance imaging (MRI) can potentially differentiate residual active tumor tissue and fibrosis. Thirty-three patients with HD or HG-NHL presenting with bulky mediastinal disease were studied with CT, 67Ga SPECT, and MRI (only for 16 patients) at diagnosis, after two-thirds of their chemotherapy, at the end of chemotherapy, and after radiotherapy in order to evaluate the mediastinal region on the basis of persistence of residual masses and activity of pathological tissue. After treatment, all patients with 67Ga-negative (30/33) disease are still in continuous complete response. Among the three 67Ga-positive patients, 2 relapsed within one year and another one is still alive without evidence of disease. Regarding MRI, two patients were found to be positive, one of them concomitant with 67Ga-positivity; both patients survive in complete response. In lymphoma patients with bulky mediastinal presentation, the 67Ga SPECT remains the preferable imaging technique for monitoring and differentiating the eventual active residual tumor. In combination, CT and 67Ga SPECT represent a suitable complete imaging approach to the radiological diagnosis which may be useful in these particular patients. MRI could probably be considered as a second-line method and from our data would be used only in selected cases because of the high cost, accessibility, and lower specificity as opposed to 67Ga SPECT in evaluating potentially active residual disease.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dacarbazine; Disease-Free Survival; Doxorubicin; Female; Fluorouracil; Gallium Radioisotopes; Hodgkin Disease; Humans; Leucovorin; Lymphoma, Non-Hodgkin; Magnetic Resonance Imaging; Male; Mediastinal Neoplasms; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Neoplasm, Residual; Prednisone; Radioimmunodetection; Radiotherapy; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Treatment Outcome; Vinblastine; Vincristine

In the last decade, there have been several reports on what is now recognized as a new clinical and pathological entity termed primarily mediastinal B-cell lymphoma (PMBCL) with sclerosis. This lymphoma presents unique clinical characteristics with an aggressive outcome and, at present, the best approach seems to be a combination of chemotherapy and radiotherapy. Between June 1989 and September 1994, twenty-two previously untreated patients with PMBCL with sclerosis were treated with a combination of third-generation chemotherapy regimen (MACOP-B or F-MACHOP) and mediastinal irradiation. All the patients presented with bulky mediastinal involvement; the radiologic clinical stage with evaluation of tumor size included computed tomography and Gallium-67-citrate SPECT. Twenty-one patients (95%) achieved a complete response and only one was resistant to treatment. Regarding 67Ga SPECT, 6 patients, including the nonresponder, showed persistent abnormal 67Ga uptake after chemotherapy; however after the mediastinal radiotherapy, all the patients except for the nonresponder were 67Ga-negative. The overall survival was 87%, with a median follow-up of 24 months from the time of diagnosis. Two of the patients who achieved complete response relapsed 7 and 10 months after completion of treatment, respectively. The relapse-free survival rate was 89% at 62 months (median 20 months). In patients presenting with bulky mediastinal PMBCL with sclerosis combined modality treatment using third-generation chemotherapy regimens and radiotherapy induces a good remission rate with greater than 80% chance of surviving disease-free, at 2 years. A longer follow-up before definitive conclusions are drawn is still warranted.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Doxorubicin; Evaluation Studies as Topic; Female; Fluorouracil; Gallium Radioisotopes; Humans; Leucovorin; Lymphoma, B-Cell; Male; Mediastinal Neoplasms; Methotrexate; Prednisone; Sclerosis; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Vincristine

A prospective randomized study on aggressive non-Hodgkin's lymphomas was conducted by investigators at several Italian institutions with the intent of comparing two third-generation conceptually different regimens: the regimen containing methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B), a short-term continuous twelve-week therapy, and F-MACHOP (5-fluorouracil, methotrexate with leucovorin rescue, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone), a monthly intensive cyclic treatment combining prednisone with six active non-cross-resistant cytotoxic drugs. The goals of this study were the response rate, relapse-free survival, and incidence of hematologic and nonhematologic toxicities. Two hundred-eighty-six patients included between 15 and 60 years fulfilled the criteria for entry to the study; 140 patients were treated with MACOP-B and 146 with F-MACHOP. The minimum follow-up was 24 months. Clinical characteristics of all patients were similar and known prognostic factors were equally distributed between the two groups. Complete remission (CR) was achieved by 61% and 67% of the patients treated with MACOP-B and F-MACHOP, respectively; 4% and 6% were primarily resistant, 2% and 5%, respectively, died of causes directly related to therapy. At 50 months, 74% of all CR patients were alive without disease and there were no significant differences in relapse-free survival between the two groups: 75% in the F-MACHOP group and 73% in the MACOP-B group at 50 months. There was a higher incidence of mucositis among patients treated with MACHOP-B than among those given F-MACHOP (11% vs 3.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Diseases; Cyclophosphamide; Cytarabine; Disease-Free Survival; Doxorubicin; Female; Fluorouracil; Humans; Italy; Leucovorin; Life Tables; Lymphoma, Non-Hodgkin; Male; Mediastinal Neoplasms; Methotrexate; Prednisone; Prognosis; Proportional Hazards Models; Prospective Studies; Remission Induction; Risk Factors; Treatment Outcome; Vincristine

Primary mediastinal B cell lymphoma is a rare entity and often should be promptly treated as a hematological emergency: The initial treatment decision is crucial for the management of this disease. An observational retrospective study was conducted with the aim to improve information on treatment and outcomes of primary mediastinal B cell lymphoma in real practice. After 12 cycles of MACOP-B regimen (methotrexate, doxorubicin, cyclophosphamide, vincristine, bleomycin , and prednisone) with or without rituximab, 120 patients out of 151 (79.5%) achieved a complete response and 12 (7.9%) a partial response leading to a global response of 87.4%. The 21-year overall survival is 82.6%; progression-free and disease-free survivals are 69.3% and 86.4%, respectively. Regarding the role of radiotherapy (RT), patients with a negative PET scan after MACOP-B did not undergo RT: One out of these 48 (2.1%) showed a relapse at 11 months. All relapsed/refractory patients who achieved a response with checkpoint inhibitors are still in continuous complete response with a median follow-up of 14 months. Data that we have gathered over a 30-year experience in the treatment of primary mediastinal B cell lymphoma patients clearly indicate that a third-generation chemotherapy regimen such as MACOP-B is feasible and easily deliverable on an outpatient basis. Regarding the unmet medical need of relapsed/refractory patients, new encouraging results occurred with the advent of the checkpoint inhibitors.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, B-Cell; Male; Mediastinal Neoplasms; Methotrexate; Middle Aged; Prednisone; Retrospective Studies; Rituximab; Treatment Outcome; Vincristine; Young Adult

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

Among 125 patients prospectively enrolled in the IELSG-26 study, 88 were eligible for central review of PET/CT scans after completion of RT. Responses were evaluated using the 5-point Deauville scale at the end of induction R-CHT and after consolidation RT. According to the Lugano classification, a complete metabolic response (CMR) was defined by a Deauville score (DS) ≤3.. The CMR (DS1, -2, or -3) rate increased from 74% (65 patients) after R-CHT to 89% (78 patients) after consolidation RT. Among the 10 patients (11%) with persistently positive scans, the residual uptake after RT was slightly higher than the liver uptake in 6 patients (DS4; 7%) and markedly higher in 4 patients (DS5; 4%): these patients had a significantly poorer 5-year progression-free survival and overall survival. At a median follow-up of 60 months (range, 35-107 months), no patients with a CMR after RT have relapsed. Among the 10 patients who did not reach a CMR, 3 of the 4 patients (positive predictive value, 75%) with DS5 after RT had subsequent disease progression (within the RT volume in all cases) and died. All patients with DS4 had good outcomes without recurrence.. All the patients obtaining a CMR defined as DS ≤3 remained progression-free at 5 years, confirming the excellent negative predictive value of the Lugano classification criteria in primary mediastinal large B-cell lymphoma patients. The few patients with DS4 also had an excellent outcome, suggesting that they do not necessarily require additional therapy, because the residual

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Disease Progression; Disease-Free Survival; Doxorubicin; Etoposide; Female; Fluorodeoxyglucose F18; Humans; Immunotherapy; Leucovorin; Liver; Lymphoma, B-Cell; Male; Mediastinal Neoplasms; Methotrexate; Neoplasm, Residual; Positron Emission Tomography Computed Tomography; Prednisone; Prospective Studies; Radiopharmaceuticals; Radiotherapy Dosage; Radiotherapy, Conformal; Recurrence; Rituximab; Statistics, Nonparametric; Vincristine; Young Adult

Our aim is to assess the incidence of second cancer in long-time surviving primary mediastinal B-cell lymphoma (PMBCL) patients treated with combined radiochemoimmunotherapy (standard methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin with rituximab and mediastinal radiation therapy at a dose of 30 to 36 Gy). For this purpose, 92 points were evaluated. After a median overall survival of 137 months (range 76-212), we recorded second cancer in 3 of 80 long-surviving patients (3.75%) with cumulative incidence of 3.47% at 15 years and 11% at 17 years, with a 17-year second cancer-free survival of 82%. We observed 2 papillary thyroid cancers with a standardized incidence ratio (SIR) of 7.97 and an absolute excess risk (AER) of 17. 84 and 1 acute myeloid leukemia (AML) with an SIR of 66.53 and an AER of 10.05. No breast cancer occurred. Although we should take into account the limits of the proposed statistical analysis, combined modality treatment was related to a significant SIR and AER for thyroid cancer and acute myeloid leukemia.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cancer Survivors; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Humans; Incidence; Kaplan-Meier Estimate; Leucovorin; Lymphoma, B-Cell; Male; Mediastinal Neoplasms; Methotrexate; Middle Aged; Neoplasms, Second Primary; Prednisone; Radiotherapy; Risk; Treatment Outcome; Vincristine; Young Adult

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

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

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 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

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

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

Six cases of mediastinal large B-cell lymphoma (MLCL) with sclerosis were analyzed for the presence and patterns of c-myc and bcl-2 loci rearrangements, and for the presence of Epstein-Barr virus DNA sequences by Southern blot hybridization, c-myc gene alterations were found in three of six cases. Two cases showed the presence of mutations or small rearrangements at the 3' end of the first exon. The c-myc gene abnormalities found in these two cases are similar to those observed in the translocation 8;14 of the endemic Burkitt's lymphomas or in its variants t(2;8) and t(8;22). A third case showed a major rearrangement of c-myc gene, with truncation within its first intron, similar to those observed in sporadic Burkitt's and in acquired immunodeficiency-associated lymphomas. None of the cases displayed bcl-2 gene rearrangements or contained viral sequences. Our data suggest a possible role for a translocation-mediated c-myc activation in the pathogenesis of MLCL. Conversely, bcl-2 gene and Epstein-Barr virus do not appear to be involved in the pathogenesis of these peculiar lymphomas. The association between c-myc structural modifications and MLCL also seems to be of relevance in light of the peculiar tendency of this tumor to involve unusual extranodal site (eg, kidney), reminiscent of the spreading attitude of Burkitt's limphomas.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chromosome Aberrations; Chromosome Disorders; Combined Modality Therapy; Cyclophosphamide; DNA Probes; DNA, Neoplasm; Doxorubicin; Female; Gene Rearrangement; Genes, myc; Humans; Leucovorin; Lymphoma, B-Cell; Male; Mediastinal Neoplasms; Methotrexate; Nucleic Acid Hybridization; Prednisone; Proto-Oncogenes; Restriction Mapping; Vincristine

Non-Hodgkin's lymphoma occurring during pregnancy is a rare event. A young woman at 18 weeks gestation with twins presented with a B-cell immunoblastic lymphoma. Combination chemotherapy with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) was instituted after limited staging. There was excellent response and the 12 weekly chemotherapy protocol was completed in 13 weeks. Twin male infants were born at 28 weeks gestation by cesarean section for premature labor. There was no evidence of any congenital malformations or hematologic suppressions. We believe this to be the first report of aggressive weekly chemotherapy during pregnancy; this approach to treatment in aggressive non-Hodgkin's lymphoma is both efficacious and safe.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Humans; Infant, Newborn; Infant, Premature; Leucovorin; Lymphoma, Non-Hodgkin; Male; Mediastinal Neoplasms; Methotrexate; Prednisone; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy, Multiple; Twins; Vincristine

We report the clinical findings of 21 consecutive patients affected by mediastinal large B-cell lymphoma with sclerosis. This type of lymphoma is a recently described histopathologic entity characterized on clinical grounds by distinctive features, which, according to our series, can be summarized as follows: young age (median, 30 years; range, 15 to 42 years), prevalence of females over males (15 v six), rare occurrence of superficial lymph node enlargement (three of 21 patients), and involvement of unusual extranodal sites (kidney six, adrenal cortex two patients). The clinical course appears to be closely related to treatment. In fact, complete remission (CR) was not obtained in the six patients submitted to conventional cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus bleomycin (CHOP-Bleo) regimens until 1985, as opposed to 13 CRs reached in the 15 patients subsequently treated with more aggressive regimens after 1985 (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B], 12 patients; methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone [M-BACOD], two patients; and vincristine, cyclophosphamide, fluorouracil, cytarabine, doxorubicin, methotrexate, and prednisone [F-MACHOP], one patient; plus involved-field radiotherapy, 10 patients). Among the 13 patients who achieved a CR, only one relapse was observed at 10 months. The median overall survival of complete responders after an observation period of 11 to 69 months has not yet been reached, and the event-free survival curve indicates that 90% of patients who achieve CR may be potentially cured.

Topics: Adolescent; Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphoma, Non-Hodgkin; Male; Mediastinal Neoplasms; Methotrexate; Neoplasm Staging; Prednisone; Remission Induction; Sclerosis; Sex Factors; Survival Rate; Vincristine

Topics: Adenocarcinoma; Female; Humans; Kidney Neoplasms; Leucovorin; Mediastinal Neoplasms; Methotrexate; Middle Aged; Tracheal Stenosis

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Dysgerminoma; Humans; Leucovorin; Male; Mediastinal Neoplasms; Methotrexate; Vincristine

Choriocarcinoma with a primary site in the chest is rarely found. Characteristically, it is seen in young men presenting with cough, gynecomastia and chest pain. The disease is invariably fatal. The presently accepted therapy (triple therapy), consisting of methotrexate, actinomycin D and chlorambucil, has been unsuccessful to date.

Topics: Adult; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Humans; Leucovorin; Male; Mediastinal Neoplasms; Methotrexate; Vincristine