Prognostic Factors and Treatment Outcome in Non-Hodgkin's Lymphoma of Waldeyer's Ring

Prognostic factors and treatment outcome of 71 patients with non-Hodgkin's lymphoma of Waldeyer's ring were analyzed retrospectively. In univariate analyses, unfavorable prognosis was associated with primary disease in the base of the tongue, stage III-IV diseases, B-symptoms, high-grade histology, T-cell phenotype, elevated serum LDH levels, decreased peripheral blood lymphocyte counts, and negative response on delayed type hypersensitivity skin reactions. Multivariate analysis showed that stage III-IV and T-cell phenotype were significant independent risk factors for death. In stage I-II lymphomas, patients with unilateral large or bilateral cervical lymph node involvement had a poorer prognosis. In stage I-II lymphomas with intermediate or high-grade histology, patients who had received radiotherapy with MTCOP-P chemotherapy (pirarubicin, cyclophosphamide, vincristine, methotrexate with leucovorin rescue, peplomycin, and predonisolone) showed significantly better 5-year disease-free survival rate compared with patients treated with radiotherapy alone.     

Radiation therapy of Waldeyer's ring lymphoma

Forty-nine patients with biopsy-proven Waldeyer's ring lymphoma were treated with radiation therapy between 1968 and 1979; 45 to 50 Gy were given to Waldeyer's ring structures with a 5- to 10-Gy boost to the primary site. Uninvolved low cervical nodes received 40 to 50 Gy. Chemotherapy was reserved for treatment failures. Actuarial 5-year survival was 53%, disease-free survival was 48%, and local control was 98%. Patients with Stage I disease fared better than patients with Stage II disease, and unilateral adenopathy conferred a better prognosis than bilateral adenopathy. When classified by the Rappaport system, nodular lymphomas had a better prognosis than diffuse lymphomas, and of the diffuse lymphomas, histiocytic lymphoma was a more lethal disease than lymphocytic lymphoma. Patients with diffuse undifferentiated lymphomas in the Rappaport system, or high-grade lymphomas in the Working Formulation, fared poorly. Most relapses were systemic, and actuarial 5-year survival after salvage was only 20%. A logical approach to the treatment of this disease can be based on these prognostic features.     

Primary colorectal lymphoma in Taiwan.

BACKGROUND. Sixteen patients with primary lymphoma of the colon and rectum were studied. METHODS. The median age of these patients was 34 years, and 13 were men. These patients often experienced abdominal pain, diarrhea, a palpable abdominal mass, weight loss, bloody stools, and tumor of the cecum. Intermediate or high-grade lymphomas occurred in 14 patients, and 5 patients had T-cell lesions. The diagnoses were established by using laparotomy in 14 patients and colonoscopic biopsy in 2 patients. Fourteen patients had surgical resections followed by chemotherapy: cyclophosphamide, doxorubicin, vincristine, and prednisolone in 10; cyclophosphamide, vincristine, and prednisolone (COP) in 2; and cyclophosphamide, vincristine, methotrexate, and prednisolone in 1 patient. Two patients underwent biopsy alone followed by chemotherapy with COP in one and chemotherapy with prednisolone in the other. RESULTS. The median follow-up time was 38 months (range, 2-82 months). Eight patients are alive with no evidence of disease (range, 10-82+ months). Six patients died of disease from 2 to 44 months after diagnosis. One patient who had no evidence of lymphoma died of esophageal carcinoma at 61 months. The median survival time was 59 months. CONCLUSIONS. The authors' experience with colorectal lymphoma in Taiwan is different from that reported from Japan and other countries. The patients of this study were significantly younger and many had T-cell lesions. Despite the frequently poor histologic types, surgical resection and adjuvant chemotherapy can result in long-term, disease-free survival in many patients with primary colorectal lymphoma.     

Clinical significance of morphologic subdivision in diffuse large cell lymphoma

Although diffuse large cell lymphomas can be morphologically divided into large cell (DLC) and immunoblastic (IBL) subtypes, the clinical significance of this subdivision remains controversial. The initial diagnostic materials from 85 patients with recorded diagnoses of diffuse large cell lymphoma who were treated at Stanford between 1975 and 1986 with cyclophosphamide, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP); methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M-BACOD); or methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy were retrospectively reviewed by a panel of hematopathologists and classified according to morphologic criteria of the Working Formulation. Based on the criterion of agreement of two of three observers, 60 patients were classified as having DLC, 19 as having IBL, and the lymphomas in 6 patients could not be additionally classified. No significant differences in complete response (CR) rate, freedom from disease progression (FFP), or overall survival were found between the DLC and IBL groups. There was also no significant difference in prognosis between DLC cases additionally subclassified as large cleaved cell (16 patients) and those with large non-cleaved cell (36 patients). Although IBL is considered to be a high-grade lymphoma, the authors concluded that it does not differ significantly in prognosis from DLC lymphoma and, therefore, does not justify a modified treatment selection based on IBL morphologic type alone. Definitive evaluation of the prognostic significance of morphologic subdivision may require a larger cohort of uniformly treated patients.     

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.     

Combination chemotherapy with cyclophosphamide, vincristine, and prednisone in advanced non-Hodgkin's lymphomas.

From July 1971 to July 1974, 58 patients with advanced non-Hodgkin's lymphomas were treated with cyclophosphamide, vincristine, prednisone (CVP) at Stanford Medical Center. Utilizing the histopathologic criteria of Rappaport el al., response to CVP was found to be significantly better in the nodular (96.6%) and the diffuse lymphocytic (100%) histologies as compared to the diffuse nonlymphocytic lymphomas (47.6%). A pathologically documented complete remission was obtained in 33.9% of patients and all but two remain disease free for periods of 2-28 months. Concurrent bleomycin was administered to 17 patients during CVP therapy and no improvement in response or median survival was noted. Prior radiation therapy delivered to 21 patients did not adversely affect their response to CVP or their survival. Splenectomy in 17 patients prior to CVP did not improve hematologic tolerance to chemotherapy except in those patients with prior radiation therapy, and there was no improvement in response to CVP or survival. CVP is effective in achieving complete remissions and extended disease-free survivals in advanced non-Hodgkin's lymphomas; both a nodular architecture and a diffuse lymphocytic histology are positive determinants for response to chemotherapy and improved median survival.     

Phase II study of cyclophosphamide (C), epirubicin (E), oncovin (O), prednisone (P), methotrexate (M) + leucovorin and bleomycin (B) (CEOP-MB) in intermediate and high grade non-Hodgkin lymphomas.

Thirty-five patients with non-Hodgkin lymphoma of intermediate or high-grade histology were treated with cyclophosphamide, epirubicin, vincristine, prednisone, methotrexate plus leucovorin and bleomycin (CEOP-MB). The complete response rate was 66%. The relapse rate of these complete responders was 39%. After a median follow-up of 3 years the median duration of complete response was 23 months and the median survival of the complete responders 52 months. The median survival of the entire group was 35.5 months. The toxicity was acceptable with no cases of congestive heart failure and no toxic deaths. Epirubicin appears to have a better therapeutic index than doxorubicin in aggressive treatment protocols in advanced non-Hodgkin lymphomas.     

ProMACE-CytaBOM: combination chemotherapy for diffuse large cell lymphoma

ProMACE CytaBOM, a polychemotherapy regimen consisting of cyclophosphamide, doxorubicin, etoposide cytozar, bleomycin, vincristine, methotrexate and prednisone was administered on an outpatient basis to six consecutive patients with diffuse large cell lymphoma. All achieved a complete remission (CR). Two have relapsed. Actuarial analysis predicts 66.7% survival and 62.5% probability of remaining in remission at 40 months post diagnosis. The side effects of ProMACE CytoBOM were tolerable and included mainly vincristine induced peripheral neuropathy, infections and mucositis. Our results are consistent with the SWOG results, reported only recently, using the same combination chemotherapy regimen in patient with intermediate and high-grade non-Hodgkin's lymphomas. We conclude that ProMACE CytaBOM represents a highly effective and easy-to-administer regimen in patients with large cell lymphoma.     

Prognostic value of the Kiel classification of malignant non-Hodgkin's lymphomas.

The aim of the present research was to evaluate the prognostic value of the Kiel classification of malignant non-Hodgkin's lymphomas. For this purpose a series of 100 consecutive, previously untreated adults with advanced malignant non-Hodgkin's lymphomas was analyzed. The median age of the patients was 54 years; 61 patients were males. Although the number of the various groups considered was limited, a statistically significant difference (p less than 0.001) was found in the median survival of patients with lymphomas of low-grade malignancy (lymphocytic, lymphoplasmacytoid, centrocytic, centroblastic-centrocytic lymphoma) and lymphomas of high-grade malignancy (centroblastic, lymphoblastic, immunoblastic lymphoma). A difference in survival (p less than 0.001) was also observed among the patients with lymphocytic lymphoma and those with centroblastic-centrocytic lymphoma, whereas no significant difference in survival was found between the histological subtypes of high-grade malignant lymphomas. Our observations support the opinion that the Kiel classification is useful in clinical practice to distinguish the histological types with a better prognosis from those with a worse one; in addition this classification appears to be of conceptual value.     

Malignant lymphomas of the thyroid: a clinical pathologic study of 35 patients including ultrastructural observations.

The clinical and pathologic findings for 35 patients with malignant lymphoma presenting in the thyroid are reviewed. The lymphomas tended to occur in females with a median age of 65 years and clinically were manifested by a mass in the neck. The majority of patients were euthyroid and thyroid scans demonstrated cold nodules. In none of the patients was there clinical suspicion of lymphoma prior to surgery. Thirty-four of the cases were histiocytic lymphomas; the one exception; a patient with nodular poorly differentiated lymphocytic lymphoma, had histiocytic lymphoma in a subsequent biopsy of the soft tissues of the neck. Although classified as histiocytic, the lymphomas had the histologic and ultrastructural features of transformed lymphocytes or immunoblasts. Lending possible additional credence to the immunoblastic nature of these lymphomas was the histologic documentation of chronic lymphocytic thyroiditis in all 27 cases where residual thyroid parenchyma remained. This relationship suggests possible evolution of thyroid lymphomas from chronic lymphocytic thyroiditis and probably is analogous to the malignant lymphomas developing in other altered immune states, including Sjogren's syndrome. In the current study the overall 5-year survival was 54%. Patients under age 65, without local soft tissue extension or regional lymph node involvement, and with stage I disease survived the longest; a nodular histologic pattern also appeared to favorably influence the prognosis. Improved staging procedures and newer modes of therapy appear essential, particularly for those patients with clinical stage II disease and with local extension to soft tissues.     

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.     

Continuous cyclophosphamide, doxorubicin, vincristine, and prednisolone. A new, innovative protocol for diffuse aggressive lymphomas

One hundred eight patients with aggressive non-Hodgkin's lymphoma (high and intermediate grade) were treated with a new protocol: continuous cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). They were evaluated for long-term survival and pretreatment characteristics predictive of response and survival. Continuous CHOP protocol consists of initial 8 weeks of intensive chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone, followed by local/cranial radiotherapy and maintenance therapy. Complete remission (CR) was achieved in 84 of 108 (78%) patients; seven (6%) had a moderate response and 17 (16%) had a poor response. A statistically significant difference in CR rate was found only in patients with different stages. Seventeen of 84 (20%) complete responders have had a relapse of the disease. The median survival has not been reached. Results show an actuarial disease-free survival (DFS) of 77% for the 84 patients who had a complete response. The overall survival for all patients was 53% at 5 years of follow-up. The difference in DFS at the end of 5 years between different stages, main histologic subgroups, and age groups was not statistically significant. The toxicity observed was acceptable. Thus continuous CHOP appears to be an effective protocol for the treatment of intermediate-grade and high-grade lymphomas.     

Non-Hodgkin's lymphoma in children.

Until recently the prognosis of childhood non-Hodgkin's lymphoma has been poor. A program of combination chemotherapy and involved area radiotherapy was instituted in the Department of Pediatrics at Roswell Park Memorial Institute in 1971. Thirty-one biopsy proven untreated children entered this study. There were 4 Stage I, 9 Stage II, 6 Stage III, and 12 Stage IV. Initial site of presentation was neck and mediastinum in 16, abdomen in 12, and other sites in three. Nineteen were lymphocytic, seven histiocytic, three undifferentiated, and one was mixed. None had well differentiated or nodular histology. Chemotherapy consisted of vincristine and steroid induction along with intrathecal methotrexate followed by a maintenance phase consisting of daily oral 6-mercaptopurine, weekly oral methotrexate and monthly pulses of vincristine, cyclophosphamide and steroid. Because of initially poor results in Stage IV disease, the protocol was altered midway and high dose methotrexate on three occasions following induction was added. Twelve of 13 Stage I and II patients remain disease free. Four of 6 Stage III patients and 4 of 12 Stage IV patients remain disease free. Only 1/7 of the Stage IV patients prior to high dose methotrexate is disease free, whereas, 3/5 patients with high dose methotrexate are disease free. In total, 19/30 (63%) are disease free for a period ranging from 15+ to 63+ months with 19 patients being disease free for over one year and 12 for over two years.     

A comparison between combination chemotherapy and total body irradiation plus combination chemotherapy in non-Hodgkin's lymphoma.

Thirty-nine untreated patients with either lymphocytic or nodular mixed/nodular histiocytic non-Hodgkin's lymphoma, stage II--IV, were randomized to treatment with total body irradiation (TBI), 100 rads in 10 fractions over 12 days, plus combination chemotherapy with either cyclophosphamide, vincristine and prednisone (CVP) or cyclophosphamide, vincristine, procarbazine and prednisone (C-MOPP) or to treatment with combination chemotherapy (CVP or C-MOPP) alone. Remission rate and duration was comparable for both treatment groups; thus the use of both treatment modalities ab initio provides no therapeutic advantage.     

Non-Hodgkin's Lymphomas in Turkey: Eighteen Years'Experience at the Hacettepe University

In this retrospective study, 470 patients with non-Hodgkin's lymphoma (NHL) who had been followed in the Hacettepe University Medical Oncology Department between 1973 and 1990, were evaluated to establish their epidemiologic, clinical and therapeutic characteristics. Out of 470 patients, 302 (62.2%) were male and 168 (37.8%) were female. The ages ranged from 16 to 85, with a median of 44 years. Constitutional symptoms were present in 46.4% of the patients. According to the Working Formulation, low, intermediate, and high-grade lymphomas comprised 33.4%, 54.9%, and 12.7%, respectively. The most common extranodal presentation was gastrointestinal. The chemotherapy regimens most commonly used were CVP (cyclophosphamide, vincristine, prednisone), BCNOP (bleomycin, cyclophosphamide, mitoxantrone, vincristine, prednisone), CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and CHOP-Bleo (cyclophosphamide, doxorubicin, vincristine, prednisone, bleomycin). The response rates and the survival figures attained with these regimens were not statistically significantly different ( P > 0.05). In the Cox multivariate model, pathologic grade, leukopenia, responsiveness to chemotherapy, bone marrow involvement and age were the important factors influencing the disease-free survival, while responsiveness to chemotherapy, age, presence of constitutional symptoms, pathologic grade, extranodal presentation and stage were the important factors influencing the overall survival. The distribution of NHL according to grade and stage was similar to that in western societies, while constitutional symptoms and lymphomas of the small intestine including immunoproliferative small intestinal disease were more common in Turkey.     

A Six-Drug Regimen (Mapeco) for Intermediate or High-Grade Non-Hodgkin's Lymphoma

Forty-eight patients with intermediate and high-grade NHL were treated with an intensive weekly six-drug regimen of methotrexate, doxorubicin, prednisolone, etoposide, cyclophosphamide and vincristine (MAPECO) between 1982-1988 and now have a median follow-up of 4.8 years. Nineteen of these patients received an intensified derivative of this regimen with the incorporation of bleomycin. Histological sub-type showed intermediate grade in 28 and high grade in 20 patients. Forty-five patients received the 4 planned cycles, and all patients achieved an objective response, of whom 36 (75%) entered complete remission. At 5 years, the actuarial survival of the 48 patients was 50%. Of the 36 patients achieving complete remission, the relapse-free survival at 5 years was 62%. The 5-year time to treatment failure was 48% for the whole group and 40% for the 22 stage III + IV patients. Histological sub-type had no effect on survival and time to failure curves. Neutropenic fever occurred in 15 patients and grade 3/4 mucositis was seen in 25. The MAPECO combination is an effective intensive regimen with acceptable toxicity for intermediate and high-grade lymphoma.     

Non-Hodgkin's lymphoma in northern India. A retrospective analysis of 238 cases

A retrospective analysis was performed of 238 patients, aged 12 years and older, with non-Hodgkin's lymphoma presenting to the All India Institute of Medical Sciences, New Delhi, India, between September 1975 and December 1982. Pathologic material was reviewed and classified according to the modified Rappaport classification. The most common histologic type encountered was diffuse histiocytic lymphoma (39%), followed by diffuse poorly differentiated lymphocytic lymphoma (29%), and diffuse mixed histiocytic and lymphocytic lymphoma (9%). Nodular lymphomas constituted 9% of all non-Hodgkin's lymphomas. A lower frequency of nodular lymphomas, a lower median age of onset (45 years), and a higher male to female ratio (4.5:1) as compared with Western countries was observed. Survival information on 90 patients revealed no effect of age, sex, stage of disease, and "B" symptoms on survival, whereas histologic diagnosis had a significant influence on survival (P less than 0.05). A median survival of 24 months in 58 patients receiving chemotherapy is comparable to that reported by other investigators.     

Mediastinal large-B-cell lymphoma with sclerosis: a clinical study of 21 patients.

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.     

Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study.

As a part of an ongoing prospective controlled trial, the Southwest Oncology Group compared the results of treatment of advanced non-Hodgkin's lymphoma with two CHOP regimens (cyclophosphamide, adriamycin, vincristine and prednisone with either low-dose bleomycin or BCG by scarification) to a COP regimen (cyclophosphamide, vincristine and prednisone) with low-dose bleomycin (COP-Bleo). The study design emphasized histopathology review and systematic restaging to define complete remission (CR). Confirmed rates of CR for 443 evaluable patients were 59% for 286 patients receiving the CHOP regimens and 59% for 157 patients receiving COP-Bleo. Rates of CR were higher for patients with nodular lymphoma (69%) compared to those with diffuse lymphoma (54%) (p = 0.005). For patients with nodular lymphoma there was no difference in CR rates according to treatment. For patients with diffuse lymphomas the CR rate was higher with the CHOP programs (58%) than with COP-Bleo (44%) (p = 0.10). Overall duration of CR and survival was significantly longer for patients with nodular lymphoma compared to diffuse lymphoma (p less than 0.01). At this time, remission duration and survival were similar regardless of induction regimen used in patients with nodular lymphoma. However, in patients with diffuse lymphoma, the duration of CR and overall survival were improved by treatment with the CHOP regimens compared to COP-Bleo (p = 0.02). Thus, in this controlled study we have demonstrated that initial combination chemotherapy employing the CHOP regimen was a superior remission induction therapy for patients with diffuse lymphoma.     

Non-Hodgkin's lymphomas in patients with human immunodeficiency virus infection. Presence of Epstein-Barr virus by in situ hybridization, clinical presentation, and follow-up.

The authors studied all patients with serologic evidence of human immunodeficiency virus (HIV) infection and malignant non-Hodgkin's lymphoma (NHL) that presented at a single hospital from 1982 to 1989. Sixteen patients were identified, all white homosexual men with a mean age of 38.2 years. Lymphoma was the initial presentation of HIV infection in 37.5%. Sixty-two percent of the cases had a high-grade NHL, 31% had intermediate-grade, and 6% (one patient) had a low-grade lymphoplasmacytoid lymphoma. Extranodal involvement was present in 43.7%, with the gastrointestinal tract and liver being the most common sites. Actuarial survival was increased by treatment with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B). Colorimetric in situ hybridization identified Epstein-Barr virus (EBV) in nine of the 14 cases hybridized. A statistically significant association of EBV with diffuse small noncleaved type (i.e., Burkitt's-like) (six of six) compared with other morphologic types (three of eight) was found (P = 0.025).