An evaluation of total nodal irradiation as treatment for stage III A Hodgkin's disease.

Between April 1969 and December 1974, 37 patients with surgically staged III A Hodgkin's disease were treated with total nodal irradiation (TNI). Their probability of relapse-free survival at 7 years is 51% and overall survival 82% with the majority of patients remaining disease free after retreatment with MOPP (10 of 16). In contrast, 21 stage III B patients treated with TNI and MOPP chemotherapy over the same time period have a relapse-free survival of 74% and overall survival of 91%. Because of superior results in treating stage III B patients with combined modality treatment, we fell that a relapse-free survival of 51% may not justify continuation of TNI as the only modality of treatment for patients with stage III A disease, and we have initiated a trial of combined radiation therapy and MOPP chemotherapy in these patients. The most effective treatment of stage III A Hodgkin's disease, however, remains uncertain and depends both on the ultimate risk of combined modality treatment and the success of retreatment following relapse after radiation.     

Combined modality therapy for mediastinal Hodgkin's disease. Prognostic significance of constitutional symptoms and size of disease

Combined modality therapy was used in an attempt to increase the complete remission rate and survival of previously untreated patients with Hodgkin's disease. MOPP (nitrogen mustard, vincristine, procabazine, prednisone) chemotherapy was followed by radiotherapy. The median duration of follow-up exceeded 5 years. Complete remissions were achieved in 63 of 71 patients (89%) with mediastinal masses. The actuarial survival of 10 years was 72% for patients with small mediastinal masses (mediastinal mass ratio less than 0.35) and 46% for patients with large mediastinal masses (P less than 0.05). The corresponding disease-free survival figures were 69% and 46%, respectively (P less than 0.05). A small mediastinal mass did not affect prognosis. Systemic symptoms especially affected the prognosis in patients with a large mediastinal mass, since in symptomatic patients the actuarial survival and freedom from relapse were 19%, whereas all asymptomatic patients survived without relapse. In patients with a small mediastinal mass, systemic symptoms had no significant effect on the actuarial survival or disease free survival. Age and stage did not affect the prognosis in patients with large mediastinal masses. It was concluded that MOPP chemotherapy followed by radiotherapy was an adequate treatment for asymptomatic patients with large mediastinal disease. However, in symptomatic patients with large mediastinal masses, this treatment was clearly inadequate.     

Stage III Hodgkin's disease: improved survival with combined modality therapy as compared with radiation therapy alone

This is a retrospective analysis of 120 patients with pathologically stage IIIA and IIIB Hodgkin's disease treated from April 1969 to December 1982. The median follow-up was 108 months. Treatment consisted of radiation therapy (RT) alone in 54 patients and combined radiation therapy and MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy (CMT) in 66 patients. Stage III patients treated with CMT have an improved actuarial 12-year survival as compared with patients treated with RT alone with MOPP reserved for relapse (80% v 64%; P = .026). The 12-year actuarial freedom from first relapse by treatment for stage III patients is 83% and 40%, respectively (P less than .0001). Improved survivals following combined modality therapy are seen for the following subgroups of stage III patients: stage III2, 66% (CMT) v 44% (total nodal irradiation; TNI), P = .04; stage III1, 97% (CMT) v 73% (TNI), P = .05; stage III mixed cellularity or lymphocyte depletion histology, 94% (CMT) v 65% (TNI), P = .007; and stage III extensive splenic involvement, 77% (CMT) v 58% (TNI), P = .02. These survival differences are not seen in patients with nodular sclerosis or lymphocyte predominance histology or in patients with minimal splenic involvement. These data indicate that the initial use of CMT in stage III Hodgkin's disease results in an improved survival as compared with initial treatment with RT with MOPP reserved for relapse. Patients with limited Stage IIIA disease may still be candidates for radiation therapy alone.     

Hodgkin's disease: is there a price for successful treatment? A 25-year experience

Three hundred-twenty patients with Hodgkin's disease (HD) were studied retrospectively to assess the impact of treatment on survival and the development of second malignant neoplasms (SMN). All stages of HD were considered. Treatment groups included XRT only, XRT + multiagent chemotherapy (MAC), XRT + single agent chemotherapy (SAC), and chemotherapy only (Chemo). MAC was subdivided into MOPP and non-MOPP regimens. Twenty-one patients developed 23 SMN, only two of which were acute leukemias. Survival was greatest for XRT only because of a large proportion of early stage HD in this group. SMN were seen in all treatment groups except Chemo only. The XRT + MAC group had a significantly elevated observed-to-expected ratio for SMN, but it was difficult to attribute this to either MOPP or non-MOPP due to very small numbers of patients. The actuarial risk of SMN for both MOPP and non-MOPP rises dramatically between 10 and 15 years, however, extrapolation cannot be done, again because of very small numbers. We conclude that there is an increased risk of SMN in patients treated aggressively for HD, but that the exact cause of SMN is difficult to determine.     

Three cycles of ABDV plus extended field radiotherapy in patients with poor prognosis early-intermediate stage Hodgkin's disease

The aim of the study was to verify the possibility of treating patients with poor prognosis early-intermediate Hodgkin's disease with a combined modality therapy consisting of three cycles of ABVD followed by extended field irradiation (EFRT). No patient had bulky mediastinum or had previously been administered chemo- or radiotherapy. At pathological restaging, 40/44 (91%) evaluable patients achieved complete responses (CR). After a ten-year followup, freedom from progression (FFP), relapse-free survival (RFS) and overall survival (OS) were 80%, 83% and 81%, respectively. Of the prognostic factors, univariate analysis showed that only stage III negatively influenced RFS, but not OS. Toxicity was mild except for subclinical mediastinal fibrosis in 32.5% of CR patients. No patient reported reduced fertility. Two cases of second neoplasms were recorded: one ameboid glioma and one thymoma, both occurring within five years after discontinuing chemo-radiotherapy. Our data suggest that three cycles of ABVD preceeding EFRT is an effective treatment for poor prognosis early-intermediate stage Hodgkin's disease; nevertheless, stage III patients and some stage II patients with unfavorable prognostic factors should be treated with a more aggressive approach.     

Treatment of stage I and II Hodgkin's lymphoma with ABVD chemotherapy: results after 7 years of a prospective study.

BACKGROUND: Chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine and darcarbacine) schedule is the standard treatment for advanced Hodgkin's lymphoma. Certain facts, including a low toxicity compared with MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin and vinblastine) and minimal potential for inducing second neoplasias or patient sterility, support the use of ABVD to treat early disease stages. In the present study, we prospectively evaluated the long-term efficacy and toxicity of six cycles of ABVD as treatment for early-stage Hodgkin's lymphoma. PATIENTS AND METHODS: From January 1990 to June 2002, 95 patients with stage I and II Hodgkin's lymphoma were treated with six ABVD cycles. Fifteen patients who met the criteria for mediastinal bulky disease also received further radiotherapy on the mediastinum. RESULTS: After six cycles, 89 patients (94%) showed a complete response (CR) and six patients (6%) showed a partial response (PR). These PRs became CRs after radiotherapy. After a median follow-up of 78 months, 14 patients had relapsed and three had died. Overall survival and progression-free survival rates at 7 years were 96% and 84%, respectively. For patients with stage IA and IIA without mediastinal bulky disease, the survival rates were 97% and 88%, respectively. CONCLUSIONS: The administration of six ABVD cycles is an effective and safe treatment in patients with stage I and II Hodgkin's lymphoma.     

Predictive value of the early response to chemotherapy in high-risk stages II and III Hodgkin's disease

A series of 60 patients with "high risk" Stage II and III Hodgkin's disease (B symptoms, or large mediastinal mass, or E lung disease) were staged without laparotomy and treated with combined modality treatment: mechlorethamine, vincristine, procarbazine, and prednisone (6 MOPP) plus radiotherapy. Patients were restaged after the first three courses of MOPP and the status of response to therapy at that time was called early response to chemotherapy (ERC). The rate of nitrogen mustard and procarbazine delivery (MRD) during the first three cycles of chemotherapy also was assessed. At the completion of the therapy patients were restaged and the final response was assessed. Fifty-two (86.7%) patients entered complete remission (CR). Forty-eight percent of the complete responders achieved CR in the first three courses of MOPP. Eight-year survival and disease-free survival (DFS) rates of the patients achieving CR were 71% and 73%, respectively. Survival and DFS were significantly better for the patients who achieved CR in the first three cycles of chemotherapy than for patients who entered CR at a later stage of therapy: 8-year survival 90% versus 55% (P = 0.00); 8-year DFS 87% versus 59% (P = 0.01). The attainment of a complete ERC was adversely affected by lymphocyte depletion (LD) histologic type (P = 0.01) and MRD less than 65% (P = 0.04). However, when a multivariate regression analysis was used, ERC was the only significant prognostic variable for survival and DFS and its predictive value was confirmed even after correction by MRD. These data suggest that the rapidity of response to chemotherapy could be an important prognostic factor in high-risk Stage II and III Hodgkin's disease.     

The adjuvant role of two cycles of MOPP and low-dose lung irradiation in stage IA through IIB Hodgkin's disease: preliminary results

Fifty-eight laparotomy-staged I and II patients with upper torso presentations of Hodgkin's disease and 8 patients with lymphangiogram-staged lower torso disease were treated with radiotherapy alone or with 2 cycles of MOPP and radiotherapy. Patients with upper torso disease with either no mediastinal or only small mediastinal disease without hilar involvement and with no "B" symptoms were treated with mantle radiotherapy alone. Patients with large mediastinal masses or hilar disease were treated with 2 cycles of MOPP followed by definitive mantle irradiation and low dose lung irradiation. Those for whom "B" symptoms were the only adverse prognostic feature received 2 cycles of MOPP and mantle radiotherapy. Patients with lower torso disease were treated with radiotherapy alone if the disease was limited to the pelvis. Those with more extensive disease received 2 cycles of MOPP prior to radiotherapy. The 4-year survival for all 66 patients was 97%. The corresponding disease-free and freedom from second relapse figures were 77% and 92%. Survival for the patients with unfavorable presentations who received 2 cycles of MOPP and radiotherapy was 100%. It was 92% for the group with favorable presentations who were treated with radiotherapy only.     

Laparotomy-staged IA versus IIA Hodgkin's disease. A comparative study with evaluation of prognostic factors for stage IIA disease

Ninety-one laparotomy-staged (LAP) IA and IIA Hodgkin's disease (HD) patients were analyzed to evaluate the prognostic significance of stage, mediastinal status, extranodal disease and histology. Forty IA patients were treated with radiotherapy (XRT) only; of 51 IIA patients, 44 received XRT only and 7 had additional chemotherapy. Disease-free survival (DFS) at 5 and 10 years was 81% and 70%, respectively, with overall survival (S) of 93% and 86%, respectively. Disease-free survival for IA patients (93% at 5 and 10 years) was significantly superior to IIA (73% at 5 years, 52% at 10 years). Survival differences were not statistically significant. For IIA patients receiving XRT only, large mediastinal disease was an adverse factor for DFS. Small mediastinal disease in IIA was significantly better than no mediastinal disease. For the whole group of LAP IA and IIA treated by XRT only, three prognostic groups were identified: (1) Stage IA and Stage IIA with mediastinal disease, but less than 7.5 cm in width was highly favorable with less than 10% relapse; (2) Stage IIA nonmediastinal had an intermediate prognosis with relapse in about 33%; (3) Stage IIA large mediastinal (greater than or equal to 7.5 cm) had an unfavorable DFS with relapse in about 55%. The third group contained a highly unfavorable subset with mediastinal masses greater than 10 cm, all of whom relapsed. Salvage therapy was successful in 60% of relapsing patients. In the context of relatively effective salvage therapy, the role of adjuvant chemotherapy in adverse prognostic groups is discussed and it is concluded that the only clearly justifiable use for adjuvant chemotherapy is in patients with massive (greater than 10 cm) mediastinal adenopathy.     

Is pelvic irradiation necessary in stage III1A Hodgkin's disease?

Eighteen patients with pathologic Stage (PS) III1A Hodgkin's disease were treated with mantle and para-aortic field radiation therapy alone between 1973 and 1988. The median follow-up time is 84 months (range 20-174 months). The 5-year survival and relapse-free survival rates are 76 and 82%. Six patients had extensive splenic involvement or bulky mediastinal adenopathy, and three have relapsed and are dead of disease. Of the other 12 patients, only one has had recurrence of disease and died. Patients with PS III1A Hodgkin's disease are good candidates for mantle and para-aortic radiation therapy only, provided that they do not have extensive splenic involvement or large mediastinal adenopathy.     

Low-dose radiation therapy and reduced chemotherapy in childhood Hodgkin's disease: the experience of the French Society of Pediatric Oncology.

PURPOSE: With the aim of decreasing undesirable side effects of therapy, we investigated the reduction of both chemotherapy and radiation therapy (RT) in children with Hodgkin's disease, and compared Adriamycin (doxorubicin; Farmitalia Carlo Erba, Rueil-Malmaison, France), bleomycin, vinblastine, and dacarbazine (ABVD) alone to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and ABVD in favorable cases and assessed the effectiveness of low-dose RT (20 Gy) after good response to chemotherapy. PATIENTS AND METHODS: A French national study began in 1982 that included 238 pediatric patients with Hodgkin's disease. Initial staging was clinical and without laparotomy. In patients with localized disease (IA-IIA), an equivalence trial compared the effectiveness of four cycles of ABVD with two cycles of ABVD that were alternated with two cycles of MOPP. Patients with more advanced disease (IB-IIB-III-IV) received three courses of MOPP that was alternated with three courses of ABVD. All of the patients who achieved a good remission after chemotherapy were administered 20 Gy RT, which was limited to the initially involved areas for localized disease, and encompassed the paraaortic nodes and the spleen as well for more advanced stages. When a good remission was not obtained, 40 Gy RT was administered. RESULTS: At the completion of chemotherapy, 227 patients (97%) were considered good responders, whereas 11 did not achieve a good remission. With a median follow-up of 6 years, the 6-year actuarial survival was 92% and the disease-free survival was 86%. The relapse-free survival in favorable stages was 90% in the ABVD arm and was 87% in the MOPP and ABVD arm. In June 1987, inclusion of stage IV patients was discontinued because of poor results. CONCLUSIONS: Present findings indicate that (1) in favorable stages, ABVD alone and alternating MOPP and ABVD are equivalent, and (2) chemotherapy followed by 20 Gy RT represents a valid therapeutic approach in the vast majority of children with Hodgkin's disease.     

Radiation therapy versus combination chemotherapy in the treatment of early-stage Hodgkin's disease: seven-year results of a prospective randomized trial

The study population included 136 patients with stage IA, IB, IIA, IIB, or IIIA1 Hodgkin's disease. The median follow-up is 7.5 years. Among the 30 patients with peripheral IA disease, all patients achieved a complete response (CR) with radiation therapy, and no patient has relapsed. Patients of other stages were randomized to receive radiation therapy or mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). Among the 51 patients randomized to receive radiation therapy, 49 (96%) achieved complete remission, 17 (35%) have relapsed, and 10 (20%) have died. Fifty-two of the 54 (96%) assessable patients randomized to receive MOPP obtained CRs, seven (13%) have relapsed, and four (7%) have died. The projected 10-year disease-free survival of patients randomized to receive radiation therapy is 60%; for those randomized to receive MOPP, it is 86% (P2 = .009 in favor of MOPP). The projected 10-year overall survival for patients randomized to radiation therapy is 76%, and for MOPP-treated patients it is 92% (P2 = .051 in favor of MOPP). When the randomized patients with massive mediastinal disease or stage IIIA1 disease were excluded from the analysis, the disease-free (67% for radiation v 82% for MOPP) and overall survival (85% for radiation v 90% for MOPP) were not significantly different between the two arms. Subset analysis showed significant superiority of MOPP in the treatment of the following patient groups: stage IIIA1 or massive mediastinal disease, no B symptoms, initial erythrocyte sedimentation rate greater than 20 mm, four or more sites of disease, and younger than age 40 years. Preliminary analysis of this ongoing study shows that MOPP chemotherapy is at least as effective as radiation therapy in the treatment of the specific groups of early-stage Hodgkin's disease patients randomized. The final assessment of these two diverse treatment options will depend largely on the long-term survival and the incidence of early- and late-treatment complications for which patients are continuing to be observed.     

Results of treatment of stage IA and IIA Hodgkin's disease

This study analyzed the 5 year actuarial survival and disease-free survival of 122 patients with Stage IA and IIA Hodgkin's disease, (108 patients laparotomy staged) treated with mantle and paraaortic irradiation from 1975 to 1981. Prognostic subgroups and patterns of treatment failure were investigated. The 5 year actuarial survival and disease-free survival was 91% and 75% respectively for the entire group. For Stage IA patients, the 5 year survival and disease-free survival was 92% and 86% respectively, whereas for those in Stage IIA the respective figures were 86% and 65%. Individuals with greater than four sites of involvement at initial presentation; extensive mediastinal adenopathy; hilar or extramediastinal extension to lung, pleura or pericardium, had a poorer 5 year actuarial disease-free survival (43%-60%) than those without these factors (70%-85%). Of the 122 patients, there were 26 relapses: nine infield failures; two concurrent infield and systemic failures; nine marginal recurrences, and three relapses occurring systemically and three in nodal groups not irradiated. Following relapse, 17 patients were salvaged with chemotherapy. Two patients are alive with disease and seven patients died of Hodgkin's disease. Patients with less extensive mediastinal adenopathy and supradiaphragmatic nonmediastinal presentations can be satisfactorily treated with mantle and paraaortic irradiation, whereas patients with extensive mediastinal adenopathy receive six cycles of multiagent chemotherapy before irradiation.     

Anatomical substages of stage III Hodgkin's disease: implications for staging, therapy, and experimental design

Twenty-three patients with pathologic stage III Hodgkin's disease were classified with respect to the presence or absence of symptoms (III-A, III-B), the presence or absence of splenic involvement (IIIS+, IIIS-) and anatomic substage--the extent of disease within the abdomen (III1, III2). Stage III1 disease included disease limited to the upper abdomen, i.e., spleen, splenic node, celiac node, and/or portal node. All other more extensive disease was classified as stage III2. Symptoms and splenic involvement did not predict either disease-free survival or survival. However, 5 year actuarial disease-free survival was significantly better in III1 patients as compared to III2 patients (77% vs. 13%, p less than .001). Eight of nine stage III2 patients receiving total nodal radiotherapy alone relapsed. When considered along the previous studies of anatomic substage, these findings suggest that patients in stage III1 and III2 should receive different therapeutic approaches. Analysis of therapeutic results in stage III patients must consider anatomic substage.     

Treatment of lower torso stages I and II Hodgkin's disease with radiation with or without adjuvant mechlorethamine, vincristine, procarbazine, and prednisone

From 1956 to 1987, 60 patients with either lymphangiogram-staged or laparotomy-staged I-II lower torso presentations of Hodgkin's disease were treated with radiation with or without Mustargen (mechlorethamine), vincristine, procarbazine, and prednisone (MOPP). In 22 with inguinal/femoral or pelvic disease and 24 with abdominal disease, treatment consisted of radiation only. Fourteen other patients with abdominal disease received MOPP chemotherapy before radiotherapy. In 11, the chemotherapy was limited to two cycles. At 10 years, the determinate survival and freedom from progression rates for all patients were 82% and 72%, respectively. For patients with inguinal/femoral or pelvic disease who were treated with radiation only, the corresponding rates were 90% and 86%. For patients with abdominal disease who received radiation only, the determinate survival and the freedom from progression rates were only 66% and 50%, respectively. However, corresponding results for 14 patients with abdominal disease who were treated with MOPP and radiation were 100% and 92% (P = 0.033 and P = 0.009, respectively.     

Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: mature results of a prospective clinical trial.

PURPOSE: To provide more mature data on the efficacy and complications of a brief, dose-intense chemotherapy regimen plus radiation therapy (RT) to bulky disease sites for locally extensive and advanced-stage Hodgkin's disease. PATIENTS AND METHODS: One hundred forty-two patients with stage III or IV or locally extensive mediastinal stage I or II Hodgkin's disease received Stanford V chemotherapy for 12 weeks followed by 36-Gy RT to initial sites of bulky (> or =5 cm) or macroscopic splenic disease. Freedom from progression (FFP), overall survival (OS), and freedom from second relapse (FF2R) were determined using life-table estimates. Outcomes were analyzed according to the international prognostic score. Late effects of treatment were recorded in follow-up. RESULTS: With a median follow-up of 5.4 years, the 5-year FFP was 89% and the OS was 96%. No patient progressed during treatment, and there were no treatment-related deaths. FFP was significantly superior among patients with a prognostic score of 0 to 2 compared with those with a score of 3 and higher (94% v 75%, P <.0001). No secondary leukemia was observed. To date, there have been 42 pregnancies after treatment. Among 16 patients who relapsed, the FF2R was 69% at 5 years. CONCLUSION: These data confirm our preliminary report that Stanford V chemotherapy with RT to bulky disease sites is highly effective in locally extensive and advanced Hodgkin's disease. It is most important to compare this approach with standard doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy in the ongoing intergroup trial (E2496) to determine whether Stanford V with or without RT represents a therapeutic advance.     

Prognostic models for Hodgkin's disease

A prognostic model for Hodgkin's disease was worked out using the data on disease-free survival among patients receiving 4-8 courses of COOP(MOPP)/ABVD plus (sub)total irradiation. Patients with stage I-II Hodgkin's disease (less then 4 lesions) without large involved mediastinal masses, intoxication symptoms and focal splenic involvement were referred to the favorable prognosis group. The poor prognosis group featured stage III(2)-IV tumor as well as large masses of involved mediastinal tissue, focal splenic involvement at any stage plus 7 or more lesions. An assessment of tumor advancement across lesions is more significant for radiotherapy planning rather than that of organ involvement. It is reasonable to distinguish two substages--III(1) and III(2). Our model was compared with GHSG and it was suggested that ways be found to use both of them in prognosing of disease outcome.     

Intensive chemotherapy and low-dose radiotherapy for the treatment of advanced-stage Hodgkin's disease in pediatric patients: a Pediatric Oncology Group study.

Sixty-two patients with advanced-stage Hodgkin's disease and a median age of 12 years (range, 3 to 22 years) were treated with four cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternating with four cycles of doxorubicin, vinblastine, bleomycin, and dacarbazine (ABVD) followed by low-dose radiotherapy (RT). We determined the feasibility, immediate safety, and rapidity of response of patients to this regimen, as well as the relationship between prognostic factors and the rate of complete remission (CR), event-free survival (EFS), and overall survival. Therapy was well tolerated, and the major toxicity was hematopoietic. At the end of chemotherapy, 54 of 62 patients (87%) were in CR by clinical restaging, with a biopsy of residual disease where necessary. The actuarial 3-year EFS is 77% (SE, 11%), with a median follow-up of 35 months, and the survival is 91% (SE, 7%). With respect to EFS, female patients and those with stage II or III disease fared statistically better than males and patients with stage IV disease, respectively. Six patients have died: three of progressive Hodgkin's disease, one of secondary acute myelocytic leukemia (AML), one of secondary non-Hodgkin's lymphoma (NHL), and one of overwhelming bacterial sepsis. The Pediatric Oncology Group (POG) is currently engaged in a randomized study of these eight cycles of chemotherapy with and without RT to assess the role of RT in achieving comparable results.     

Treatment of advanced-stage massive mediastinal Hodgkin's disease: the case for combined modality treatment

In the initial series of 198 patients treated at the National Cancer Institute (NCI) with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy for Hodgkin's disease, a review of presenting chest radiographs available on 192 of these patients showed 49 patients with mediastinal masses greater than one third the greatest posteroanterior chest diameter. Five patients had stage IIB disease, and 44 had stage III or IV disease. Thirty-five (71%) patients achieved a complete remission with MOPP chemotherapy. Fourteen (40%) of the complete responders relapsed, but four of these achieved durable remissions in response to subsequent therapy. Thirty (61%) patients have died (14 induction failures, nine relapsed patients, seven complete responders in remission). Thus, with a median follow-up of 20 years (range, 15 to 23), the overall survival for the group is 39%, and the disease-free survival for the complete responders is 60%. A subset of 10 patients received mantle radiation therapy after maximal response to MOPP. One of these patients failed to achieve complete remission, but among the nine complete responders only one has relapsed. In contrast, 13 of 26 (50%) patients achieving a complete response to MOPP alone have relapsed (P2 = .0536). Although MOPP alone was not prospectively compared with MOPP plus radiation therapy in the treatment of advanced-stage massive mediastinal Hodgkin's disease in this series, the retrospective analysis shows a nearly significant difference in disease-free survival favoring combined modality treatment. The difference in tumor mortality between MOPP-treated (44%) and combined modality-treated patients (80%) was also nearly significant (P2 = .055). However, overall survival differences between patients treated with MOPP alone and those treated with combined modality therapy were not significantly different (P2 = 0.23) because of the mortality related to late complications of combined modality treatment.     

British National Lymphoma Investigation randomised study of MOPP (mustine, Oncovin, procarbazine, prednisolone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin's disease--long term results

From 1979-1983, 299 patients with stage III or IV Hodgkin's disease (HD) were randomised to receive cyclical chemotherapy with MOPP (mustine, Oncovin, procarbazine, prednisone) or LOPP (Leukeran substituted for mustine). Two hundred and ninety patients were evaluable. There was no statistically significant difference between the complete remission (CR) rates (63% for MOPP, 57% for LOPP), percentage of patients remaining disease free at 5 years (38% for MOPP, 35% for LOPP) and overall survival at 5 years (65% for MOPP, 64% for LOPP). On multivariate analysis younger age, grade I histopathology, absence of systemic symptoms, and normal albumin level were favourable prognostic factors for survival. Acute toxicity in the form of nausea/vomiting, myelosuppression, and phlebitis were less with LOPP than MOPP. Deaths in both groups were usually due to disseminated Hodgkin's disease; there were no infective deaths in the absence of Hodgkin's disease. Second malignancies occurred in six patients treated with MOPP--three acute myeloid leukaemia (AML), one non-Hodgkin's lymphoma (NHL), two carcinomas (Ca); with LOPP, four second malignancies occurred (one AML, one NHL, two Ca). These long term results confirm that LOPP is as effective as MOPP, and less toxic, in the treatment of advanced Hodgkin's disease.