The m-BACOD combination chemotherapy regimen in large-cell lymphoma: analysis of the completed trial and comparison with the M-BACOD regimen.

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).     

CHOP with high dose cyclophosphamide consolidation versus CHOP alone as initial therapy for advanced stage,indolent non-Hodgkin's lymphomas

The role of high dose therapy, including autologous stem cell transplantation (ASCT) in indolent non-Hodgkin's lymphomas remains controversial. We evaluated a dose intense regimen of CHOP induction followed by high dose cyclophosphamide consolidation (CHOP-HC) versus CHOP alone in a prospective comparison to assess intensified therapy without ASCT. Twenty-five patients with previously untreated advanced stage indolent NHL were enrolled: follicular lymphoma, grade 1 (11 patients) and grade 2 (8 patients); small lymphocytic lymphoma (5 patients); and lymphoplasmacytic lymphoma (1 patient). All patients were treated as clinically indicated. The median age was 47 years (21-70). There were 15 males, and 10 females. Three patients had intra-abdominal stage II, 2 patients with stage III, and 20 patients with stage IV disease. All patients received induction with CHOP for 4 cycles (weeks 1,4,7,10): cyclophosphamide 750 mg/m 2 IV, doxorubicin 50 mg/m 2 IV, vincristine 1.4 mg/m 2 IV (2 mg capped dose) and prednisone 100 mg PO ×5 days. Following induction, responding patients were given consolidation with either high dose cyclophosphamide @ 3 gm/m 2 IV for 3 doses with G-CSF (weeks 13,15,17) or 2 additional cycles of CHOP (weeks 13,16), stratified by stage and bulk of disease. The overall response rate to CHOP was 92% (3 CR, 8 PR) and to CHOP-HC was 93% (4 CR, 8 PR). The overall response, complete response and partial response rates were comparable in both arms. Median progression free survival for CHOP was 15.9 and 23.0 months for CHOP-HC. At 74.3 months median follow-up, all patients in the CHOP arm have recurred; 3 patients in the CHOP-HC arm (3 CR) have not recurred. The median overall survival has not been reached (at 5 years, 77% OS for CHOP-HC versus 83% OS for CHOP alone]. Greater hematologic toxicity was observed with CHOP-HC resulting in an increased number of hospitalizations for sepsis. There were no treatment-related deaths. No myelodysplasia or acute leukemia has been seen to date. With no obvious improvement in CR and with greater hematologic toxicity than CHOP, CHOP-HC is not recommended for treatment of indolent non-Hodgkin's lymphomas.     

Low-dose ACOP-B and VABE: weekly chemotherapy for elderly patients with advanced-stage diffuse large-cell lymphoma.

Elderly patients with advanced-stage diffuse large-cell lymphomas (DLCLs) are either excluded from or under-represented in most clinical trials of combination chemotherapy regimens because they tolerate treatment poorly and usually have a worse outcome. We report two brief weekly chemotherapy regimens designed specifically for elderly patients. Eligible patients were aged 65 to 85 years, had advanced-stage DLCL (diffuse mixed, diffuse large-cleaved or noncleaved, immunoblastic, or diffuse large-cell not otherwise specified). Advanced stage was defined as Ann Arbor stage III or IV or stage I or II with a mass greater than 10 cm or B symptoms. Low-dose doxorubicin, cyclophosphamide, vincristine, bleomycin, and prednisone (LD-ACOP-B) accrued 40 patients between March 1983 and September 1985; 65% achieved a complete response (CR), there were two toxic deaths, the actuarial failure-free survival (FFS) is 19%, disease-specific survival (DSS) 30%, and overall survival (OS) 28%, with a maximum follow-up of 6 years. The regimen of etoposide, doxorubicin, vincristine, bleomycin, and prednisone (VABE) accrued 32 patients between July 1985 and June 1987; 63% achieved a CR, there were two toxic deaths, and the actuarial FFS is 34%, DSS 45%, and OS 36%, with a maximum follow-up of 4 years. There is no difference in FFS, DSS, or OS between these two regimens. VABE caused more myelosuppression and infectious complications, although the toxic death rates were similar. We prefer LD-ACOP-B because follow-up is longer and toxicity is less.     

Treatment of Diffuse Histiocytic and Diffuse Mixed Non-Hodgkin Lymphomas with Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (Chop)

During 1977 to 1985 90 patients with large-cell non-Hodgkin lymphoma (diffuse histiocytic or diffuse mixed according to Rappaport classification) were treated by the CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) with a mean follow-up of 41 months. Thirty-four patients were treated with radiation therapy as well. The mean number of CHOP cycles to achieve complete response was 4.0 and the mean total number of cycles was 6.6. For 78 patients it was possible to calculate relative dose intensity (RDI) for each drug and the average RDI. Sixty-four patients (71%) achieved CR. The actuarial 5-year survival rate of all patients was 52%. The median RDI for cyclophosphamide was 0.72, for doxorubicin 0.70, for vincristine 0.69 and the median average RDI was 0.69. The following favorable prognostic factors were found to be of statistical significance: female sex and stages I-III as compared to stage IV. The 5-year survival rate for stage I & II patients treated by CHOP plus radiotherapy was 70% as compared to 55% for those treated by CHOP only; this difference was not statistically significant.     

Patterns of relapse in large-cell lymphoma patients with bulk disease: implications for the use of adjuvant radiation therapy

In patients with large-cell lymphoma (LCL) treated with combination chemotherapy, the presence of bulk disease has consistently been associated with a poorer response rate and a shortened survival. The optimal therapy for patients with bulk disease (greater than or equal to 10 cm) will depend on whether treatment failures result from inadequate tumor eradication in prior bulk sites or from distant dissemination. To address this issue, we have evaluated patterns of relapse in patients with bulk disease who relapsed after achieving a complete remission with methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M- or m-BACOD). Eighty-one II, III, or IV patients with disease greater than or equal to 10 cm were identified; 45 of the 81 patients achieved a confirmed complete response (CR) and are included in the analysis. The 45 complete responders included 21 patients with localized (stage II) disease and 24 patients with advanced (stage III/IV) disease. Six of the 21 stage II complete responders and three of the 24 stage II/IV complete responders also received adjuvant radiation therapy following completion of M- or m-BACOD. Only one of the 21 patients with stage II disease relapsed, doing so in the site of prior bulk involvement. In contrast, nine of 24 patients with stage III/IV disease relapsed, although no patient failed solely in the site of prior bulk disease. Stage III/IV patients recurred in either a new site (one patient), a new and old site (five), an old non-bulk site (two), or both old non-bulk and bulk sites (one). These results indicate that advanced-stage bulk-disease patients do not consistently relapse in sites of prior bulk disease; therefore, this group of patients is unlikely to benefit from adjuvant radiation therapy administered following completion of combination chemotherapy. Although the low relapse rate and the addition of adjuvant radiation therapy in a subgroup of the stage II bulk-disease patients precludes a definitive analysis, our results further suggest that these patients may be effectively treated with combination chemotherapy alone.     

A 10-year update of CHOP-Bleo in the treatment of diffuse large-cell lymphoma

Long-term follow-up results of two studies using cyclophosphamide, doxorubicin, vincristine, and prednisone plus bleomycin (CHOP-Bleo) for the treatment of diffuse large-cell lymphoma are presented. Twenty-eight patients were treated with conventional-dose CHOP-Bleo and 36 patients with maximally tolerated doses of CHOP-Bleo. The maximal duration of follow-up was 10.5 years. The minimum follow-up was 5.7 years. Seventy-five percent of the conventional-dose group achieved a complete remission (CR) with a 10-year actuarial survival of 53% and a corresponding relapse-free survival (RFS) of 69% for CRs. Eighty-one percent of the high-dose group achieved CR, and the 10-year actuarial survival for all patients and RFS for CRs were 48% and 63%, respectively. The combined actuarial survival and RFS for both groups were 51% and 66%, respectively, at 10 years. For 11 patients with stage III disease, 91% achieved CR, 52% survived at 10 years, and the RFS was 67% for CRs. Seventy-five percent of 44 patients with stage IV disease achieved CR, 50% survived at 10 years, and the RFS was 67% for CRs. Three of the 16 relapses occurred late, between 30 to 65 months after initiation of therapy. Neuropathy occurred in 14 patients (22%). Five patients (8%) died of complications related to treatment. Five (8%) had clinically apparent, but nonfatal cardiopulmonary complications. The CHOP-Bleo regimen is an effective treatment for diffuse large-cell lymphoma, and is moderately well tolerated. The use of high-dose CHOP-Bleo for induction therapy did not result in any advantage after long-term follow-up.     

Intensive chemotherapy for adult lymphoblastic lymphomas

Summary A total of 20 adults patients presenting with previously untreated lymphoblastic lymphoma underwent an intensive chemotherapy protocol. Either the BACOP or the m-BACOD regimen was used for induction. If the patients achieved a complete clinical remission (CR) after three courses, they were given intensive consolidation and maintenance chemotherapy based on a protocol that was modified from the L10/L17M regimen of the Memorial Sloan-Kettering group for acute lymphoblastic leukaemia and lymphoblastic lymphoma. Patients exhibiting localised areas of bulky disease were given additional involved-field ratiotherapy. In all, 15 (75%) men and 5 (25%) women were entered in this study. Their median age was 28 years (mean, 30 years; range, 12–64 years). Overall, 3 (15%) had stage II disease, 3 (15%) had stage III disease and 14 (70%) had stage IV disease; 7 (35%) patients exhibited B symptoms and 4 (20%) had bulky disease. The overall (CR) rate was 10/20 (20%), and that following BACOP and m-BACOD therapy was 4/8 (50%) and 6/12 (50%), respectively. In all, 7 of the 10 complete responders (70%) relapsed. The disease-free survival of the ten who achieved a CR was 23% at 3 years. The overall survival of all 20 patients at 3 years was only 37%, and there were very few long-term survivors. More effective treatment for adult lymphoblastic lymphoma is required.     

COPBLAM III: infusional combination chemotherapy for diffuse large-cell lymphoma

COPBLAM III, a polychemotherapy regimen consisting of cyclophosphamide, infusional vincristine, prednisone, infusional bleomycin, doxorubicin, and procarbazine, was administered to 51 patients with diffuse large-cell lymphoma. Ninety-six percent of patients age 60 or younger achieved a complete response (CR); none have relapsed. Overall, 88% of patients are alive and well and potentially in the survival plateau. For patients greater than 60 years, CR was obtained in 73%, with 42% potentially in the survival plateau, the difference resulting in part from four relapses, three toxic deaths, and one presumed unrelated death. These results in the elderly were paralleled by a relatively reduced ability to tolerate therapy. Toxicity was primarily pulmonary, occurring in 39% of patients, two of whom died. With an overall CR rate of 84%, of which 92% are sustained at a median follow-up of 40 months, COPBLAM III represents a highly effective treatment in a sizeable cohort of patients.     

Failure of combination chemotherapy of advanced follicular (low-grade) non-Hodgkin's lymphoma

Twenty-two patients with Stage III and IV follicular non-Hodgkin's lymphoma were treated for 8 months by a chemotherapy regimen alternating between two different four-drug combinations (doxorubicin, teniposide, cyclophosphamide, prednisone; vincristine, cyclophosphamide, CCNU, prednisone). The overall response rate (complete and partial remission) was 68%. The complete remission rate was 23%. Twenty patients are alive, 50% of them are free of disease progression (median follow-up 76 months). It is concluded that our chemotherapy regimen is not satisfactory and that new therapeutic approaches are needed.     

Randomized comparison of cisplatin/vincristine/fluorouracil and cisplatin/continuous infusion doxorubicin for treatment of pediatric hepatoblastoma: A report from the Children's Cancer Group and the Pediatric Oncology Group.

PURPOSE: Previous studies demonstrated that chemotherapy with either cisplatin, vincristine, and fluorouracil (regimen A) or cisplatin and continuous infusion doxorubicin (regimen B) improved survival in children with hepatoblastoma. The current trial is a randomized comparison of these two regimens. PATIENTS AND METHODS: Patients (N = 182) were enrolled onto study between August 1989 and December 1992. After initial surgery, patients with stage I-unfavorable histology (UH; n = 43), stage II (n = 7), stage III (n = 83), and stage IV (n = 40) hepatoblastoma were randomized to receive regimen A (n = 92) or regimen B (n = 81). Patients with stage I-favorable histology (FH; n = 9) were treated with four cycles of doxorubicin alone. RESULTS: There were no events among patients with stage I-FH disease. Five-year event-free survival (EFS) estimates were 57% (SD = 5%) and 69% (SD = 5%) for patients on regimens A and B, respectively (P =.09) with a relative risk of 1.54 (95% confidence interval, 0.93 to 2.5) for regimen A versus B. Toxicities were more frequent on regimen B. Patients with stage I-UH, stage II, stage III, or stage IV disease had 5-year EFS estimates of 91% (SD = 4%), 100%, 64% (SD = 5%), and 25% (SD = 7%), respectively. Outcome was similar for either regimen within disease stages. At postinduction surgery I, patients with stage III or IV disease who were found to be tumor-free had no events; those who had complete resections achieved a 5-year EFS of 83% (SD = 6%); other patients with stage III or IV disease had worse outcome. CONCLUSION: Treatment outcome was not significantly different between regimen A and regimen B. Excellent outcome was achieved for patients with stage I-UH and stage II hepatoblastoma and for subsets of patients with stage III disease. New treatment strategies are needed for the majority of patients with advanced-stage hepatoblastoma.     

Unfavorable histologies of non-Hodgkin's lymphoma treated with ProMACE-CytaBOM: a groupwide Southwest Oncology Group study.

Chemotherapy using cyclophosphamide, doxorubicin, etoposide, cytarabine, bleomycin, vincristine, methotrexate with leucovorin, and prednisone (ProMACE-CytoBOM) for patients with intermediate- and high-grade non-Hodgkin's lymphomas was tested by the Southwest Oncology Group (SWOG) to confirm the activity of the regimen and to test the feasibility and safety of administering third-generation drug regimens in a cooperative group setting. On day 1, cyclophosphamide, doxorubicin, and etoposide were administered, followed by cytarabine, bleomycin, vincristine and methotrexate with leucovorin given on day 8. There were 51 complete remissions (CRs) among 78 previously untreated patients (65%) having clinical stage II-IV disease. The median length of follow-up is 37.9 months with 57% of patients alive at 3 years and 50% of CR patients free of disease at 3 years. Patients with diffuse large-cell lymphoma have the best survival (63% at 3 years) and relapse-free survival (RFS; 68% at 3 years with no relapses seen after 14 months). Administration of ProMACE-CytoBOM is feasible and safe in a cooperative group setting with 84% of 537 courses of treatment given exactly according to schedule and fatal toxicities seen in five patients (6%). ProMACE-CytaBOM may represent improved treatment for diffuse large-cell lymphoma, but the modest differences compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) indicate the need for a prospective randomized comparative trial.     

Prospectively randomized clinical trial of three intensive chemotherapy regimens for the treatment of advanced unfavorable histology non-Hodgkin's lymphoma

Three hundred thirty-two eligible patients with advanced (Ann Arbor stage III or IV) non-Hodgkin's lymphoma of aggressive histologic subtype (Rappaport classification diffuse histiocytic [DH], diffuse poorly differentiated lymphocytic [DPDL], diffuse mixed [DM], or diffuse undifferentiated [DU]) were randomly assigned to receive induction chemotherapy with one of three intensive regimens in a clinical trial conducted by the Eastern Cooperative Oncology Group (ECOG) between 1978 and 1983. Chemotherapy regimens consisted of cyclophosphamide, vincristine, prednisone, and doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) (COPA) administered in 3-week cycles; cyclophosphamide plus doxorubicin plus prednisone beginning day 1, with vincristine plus bleomycin day 15 of each 3-week cycle (COPA + Bleo); or cyclophosphamide plus doxorubicin plus procarbazine beginning day 1, and bleomycin plus vincristine plus prednisone beginning day 15 of each 4-week cycle (CAP-BOP). The median patient follow-up from study entry for patients still alive is 5 years. The three regimens were not significantly different with respect to complete response (CR) rates (43% to 46%), time to progression of malignant disease (median, 1.0 to 1.7 years), or survival (5-year survival, 34% to 45%), although duration of complete remission appeared to be shorter in patients receiving COPA (P = .03). COPA + Bleo and CAP-BOP were significantly more toxic than the COPA regimen. This study did not demonstrate any substantial therapeutic advantage associated with the addition of a fifth or sixth chemotherapy drug, or with treatment administered on a more frequent administration schedule, compared with the COPA regimen in this population of patients with advanced diffuse non-Hodgkin's lymphoma. The relatively small proportion of long-term disease-free survivors treated with COPA underscores the need for prospective clinical trials of new and more effective treatments for patients with these potentially curable tumors.     

Sequential Combination Chemotherapy (Caboppivim) for the Treatment of High-Grade Malignant Non-Hodgkin Lymphoma

In 42 patients with high-grade malignant non-Hodgkin lymphomas, a new treatment program was used in an attempt to improve results without increasing toxicity. Two effective but relatively well tolerated and non-cross resistant drug combinations were given sequentially according to the response of disease. Therapy was started with a combination consisting of cyclophosphamide, doxorubicin, bleomycin, vincristine, procarbazine and prednisone (CABOPP). in patients with complete remission after a maximum of 4 cycles of CABOPP, this regimen was continued for a total of 6 cycles. in patients with progressive disease or with only a partial remission after 4 cycles of CABOPP, therapy was switched to a combination consisting of etoposide, ifosfamide and methotrexate (VIM). Complete remission (CR) was achieved in 86% of patients. Sixty-nine percent achieved CR with CABOPP alone and 17% after changing to VIM. the CR rate was 100% in patients with stage I or II and 78 % in those with stage III or IV of disease. the projected survival at 2 years is 66%. Fifty-six percent of patients with CR are predicted to have continued CR at 2 years. Thus, CABOPP/VIM appears to be an effective and well tolerated program for the treatment of aggressive lymphomas. the value of this program, however, can only be established comparing it with other newly developed protocols in randomized studies.     

High-dose consolidation therapy with autologous stem cell rescue in stage IV breast cancer

We designed a phase II study to determine whether induction chemotherapy (CT) consisting of leucovorin, vincristine, methotrexate, doxorubicin, and cyclophosphamide (LOMAC) followed by high-dose intensification chemotherapy (ICT) with cyclophosphamide, thiotepa, and autologous stem cell rescue (ASCR) could increase the complete response (CR) rate and survival in women with stage IV breast cancer. Twenty-nine women were enrolled on study; 16 patients had received prior adjuvant chemotherapy and no patient had received chemotherapy for stage IV disease. Two patients were found to be ineligible and excluded from further analysis. Of the 27 patients treated, four (15%) obtained a CR and 15 (56%) a partial response (PR) after LOMAC induction, for an overall response rate of 70%. Of the 22 patients treated with ICT, 12 patients had a CR, and nine were in PR after induction and converted to CR after ICT. The toxicities included nausea/vomiting, mucositis, diarrhea, dermatitis, alopecia, and infections secondary to neutropenia. The 1-year survival is 60%; the median has not yet been reached. The time to treatment failure for patients on study is 10 months. The treatment approach of ICT and ASCR following induction chemotherapy can lead to an improved CR rate in stage IV breast cancer. How this increased CR rate leads to a prolonged disease-free survival requires further follow-up.     

Copp chemotherapy for elderly patients with intermediate and high grade non-Hodgkin's lymphoma

One hundred and forty-one consecutive patients above and 231 below the age of 60 years with previously untreated intermediate or high grade non-Hodgkin's lymphoma were included in this study. Patients above the age of 60 years were treated with the COPP chemotherapy regimen. The younger patients, at or below the age of 60, received a doxorubicin-containing regimen (119 had CHOP, 65 had BACOP and 47 had m-BACOD). For stage I patients, the clinical results were similar but for stage II, III or IV disease, those receiving COPP had significantly worse CR rate and survival than those who had a doxorubicin-containing regimen. Multivariate analysis on patients receiving the COPP chemotherapy revealed that the independent prognostic variables significantly determining CR rate and survival included clinical stage (p =0·04) and serum lactate dehydrogenase level (p =0·001). Myelosuppression was the major toxicity following COPP chemotherapy in this group of patients. There were 10 (7 per cent) treatment-related deaths. Compared to the reported results using doxorubicin-containing regimens to treat elderly patients with aggressive NHL in the literature, the more aggressive treatment does not appear to improve significantly the clinical outcome of this group of patients and seems to produce treatment results very much similar to COPP. However, accurate comparison is difficult because of the variation in the patient characteristics. Further prospective controlled randomized trials will be necessary to determine the optimal therapy for these patients.     

Rituximab Combined With MACOP-B or VACOP-B and Radiation Therapy in Primary Mediastinal Large B-Cell Lymphoma: A Retrospective Study

BackgroundThird-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.Patients and MethodsRetrospectively, 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.ResultsTwenty-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.ConclusionIn 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.     

m-BACOD treatment for intermediate- and high-grade malignant lymphomas: a Southwest Oncology Group phase II trial.

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.     

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

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

Progress in the prognosis of adult Hodgkin's lymphoma in the past 35 years through clinical trials in Argentina: a GATLA experience

The purpose of this study was to evaluate the trends in complete remission (CR) rate, disease-free survival (DFS), and overall survival (OS) through 35 years of Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) clinical trials. A total of 1,254 adult patients with Hodgkin's Lymphoma were evaluated according to seven consecutive protocols. This 35-year study was divided into three phases. The patients in the first phase (1968-1985) were treated with CVPP (cyclophosphamide/vinblastine/procarbazine/prednisone) plus involved-field radiotherapy (IFRT). In the CVPP regimen, cyclophosphamide and vinblastine were administered intravenously on day 1 and prednisone and procarbazine were administered orally on days 1-14 every 28 days. The second phase (1986-1996) used mainly reinforced CVPP with cyclophosphamide and vinblastine on days 1-8 plus IFRT. The third phase (1997-2003) used ABVD(doxorubicin/bleomycin/vinblastine/dacarbazine) plus IFRT. In clinical stage I/II, the CR rate was 86% in 252 patients treated in the first phase and DFS and OS were 57% and 78% at 5 years and 50% and 71% at 10 years. The second phase had 148 patients with clinical stage I/II disease, and the CR rate was 91%, 5-year DFS and OS were 78% and 90%, and 10-year DFS and OS were 70% and 83%. The third phase had 182 patients with clinical stage I/II disease, and the CR rate was 95%, 5-year DFS and OS were 87% and 96%, and 10-year DFS and OS were not reached. The statistical difference was P = 0.016 in terms of CR and P < 0.001 in terms of DFS and OS. In the first phase of 394 patients with clinical stage III/IV disease, the CR rate was 71%, DFS and OS at 5 years were 37% and 62%, and DFS and OS at 10 years were 32% and 53%. In the second phase of 164 patients with clinical stage III/IV disease, the CR rate was 84%, DFS and OS at 5 years were 66% and 80%, and DFS and OS at 10 years were 60% and 75%. In the third phase of 114 patients with clinical stage III/IV disease, the CR rate was 88% and DFS and OS at 5 years were 60% and 90%. The DFS and OS were not reached at 10 years. The differences among the 3 phases in CR, DFS and OS were highly significant (P < 0.001).     

Stage III follicular lymphoma: durable remissions with a combined chemotherapy-radiotherapy regimen

From 1975 to 1982, 74 patients with stage III follicular lymphoma were treated with a combined modality protocol which included chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo), and radiotherapy to involved regions. This program resulted in a complete remission (CR) rate of 81%, a 5-year survival of 75%, and 5-year relapse-free survival (RFS) of 52% for all patients. Analysis of potential factors affecting treatment outcome revealed a significantly better CR rate for patients with small cleaved cell type (97%) than for patients with mixed (73%) or large-cell (57%) histologies. The 5-year survival was significantly better for patients with small cleaved (91%) and mixed (84%) cell types than for large cell (40%). In addition, bulky abdominal disease and elevated serum lactate dehydrogenase (LDH) were significant adverse prognostic factors for CR and for survival. Toxicity was moderate. No secondary leukemias have occurred. This combined modality regimen resulted in prolonged remission and potential cure for over half of patients who achieved CR, and is particularly encouraging for those with follicular small cleaved and mixed histologies.