Combination chemotherapy with adriamycin, cyclophosphamide, vincristine, prednisolone (VEPA) in non-Hodgkin's lymphoma, with special reference to correlation of surface phenotype with response and survival

Thirty-seven previously untreated patients with advanced non-Hodgkin's lymphoma were treated with VEPA therapy. The complete remission (CR) rate was higher in the patients with diffuse B-cell lymphoma (75%) than in those with follicular B-cell lymphoma (20%) and T-cell lymphoma (42%). Two characteristics, i.e., elevated LDH and bone marrow involvement, were negatively associated with response rate in patients with diffuse lymphoma (B-, T-). The median duration of CR has not yet been reached, and the 2-year relapse-free rate was 64% for cases of diffuse B-cell lymphoma, while for T-cell lymphoma patients, the median duration of CR was 7 months. For diffuse B-cell lymphoma patients, the median survival has not yet been reached, and the 2-year survival rate was 57%. On the other hand, median survival for T-cell lymphoma patients was 12 months. VEPA therapy was less effective for the treatment of T-cell lymphoma, and a more intensive regimen should therefore be designed to overcome the potential aggressiveness of T-cell lymphoma.     

Difference in Prognosis between T- and B-Cell Lymphomas: Clinical Study at Shikoku Cancer Center Hospital

In order to determine whether the surface marker phenotypesof non-Hodgkin's lymphomas affect the prognosis, we have studiedthe differences in response rate and duration of survival betweenT- and B-cell lymphomas. Sixty-four patients who underwent first-linetherapy, including combination chemotherapy and/or radiotherapy,from February 1979 to August 1985 were evaluated. With the aidof standard immunological methods and monoclonal antibodiesrelated to T-cells and B-cells. 21 T-cell lymphomas and 21 B-celllyrnphomas were identified. In the other 22 cases phenotypeswere not determined mainly because of the inability to obtainfresh samples. The complete remission rate was 100% for B-celllymphomas and 52.3% for T-cell lymphomas. The median survivaltime for patients with lymphomas of Stage III and IV. excludingthose with low-grade histology, was nine months for T-cell lymphomasand 17 months for B-cell lymphomas. T-cell lymphomas were foundto have significantly poorer prognosis than B-cell lymphomas.One patient with B-cell lymphoma and six patients in an undeterminedphenotype group, who were treated with combination chemotherapy,have been alive more than three years without relapse and thesepatients are considered potentially cured. Our results suggestthat the surface marker phenotype study of lymphoma cells aswell as histological subtying is important in prognosis andthat more effective therapy is needed to improve the prognosisof T-cell lymphomas.     

Immunologic, Clinicopathologic and Prognostic Features of Lymphoma of the Gastrointestinal Tract

The lymphoma cells of 32 patients with histopathologically provenmalignant lymphomas with gastrointestinal (G-I) tract involvementwere examined for their surface marker characteristics. Twelvecases were diagnosed as primary lymphoma of the G-I tract and20 cases as secondary lymphoma of the G-I tract according toclinical and autopsy findings. Only one of the primary G-I tractlymphomas was identified as T-cell type, seven as B-cell typeand four as surface immunoglobulin (S-Ig)-negative non-T type(defective B-cell type). Ten of the 11 cases of non-T cell typewere histopathologically diagnosed as diffuse large lymphoidlymphoma, and one as diffuse medium-sized or poorly differentiatedlymphocytic lymphoma. This suggests that most primary G-I tractlymphoma would be large lymphoid lymphoma, even if it couldbe found at an early stage. The histopathological diagnosisof one case of T-cell type was controversial lymphocyte depletionof Hodgkin's disease or pleomorphic lymphoma is most probable. Three of the 20 secondary G-I tract lymphomas were identifiedas T-cell type, eight as B-cell type, five as defective B-celltype and four as S-Ig-undetermined non-T cell type. In contrastwith the primary G-I tract lymphomas, all histologic types wereincluded in the secondary G-I tract lymphomas. The period fromonset to G-I tract involvement ranged from four to 88 mo withan average of 32.6 mo. The tumor mass in the G-I tract in B-celllymphoma was usually large enough to be able to be detectedclinically, while a large proportion of the G-I tract lesionsin defective B-cell lymphoma and T-cell lymphoma were so smallthat they were detected only at autopsy. These results suggestthat B-cell lymphoma has a higher incidence of G-I tract involvementand a more pronounced capacity to proliferate in the G-I tractthan defective B-cell lymphoma and T-cell lymphoma. The prognosis for the patients with G-I tract lymphoma variedaccording to the stage at the time of the first examination.All three patients with stage I primary lymphoma of the G-Itract are surviving, while only three of nine patients withstage II or higher are still alive. In the case of secondaryG-I tract lymphoma, although the median survival time of stageI patients was fairly long (66 mo). more than 80% of the patientsdied of the disease. Half of the patients with stage I diseasedied within 6 mo and about 40% of the patients died within 1mo after G-I tract involvement. This indicates that secondaryG-I tract involvement of lynaphoma is a poorer risk factor forprognosis than is primary G-I tract lymphoma.     

Combination chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisolone (VEPA) for non-Hodgkin's lymphoma

Combination Chemotherapy with Adriamycin (VEPA) was applied to 16 patients with non-Hodgkin's lymphoma. The effects of VEPA therapy were compared with those of combination chemotherapy without Adriamycin (non-VEPA). Complete remission rate achieved with VEPA therapy was 37.5% while that with non-VEPA therapy was 27.6%. Histologically, the complete remission rate in cases of large-cell type treated with VEPA therapy was 40%, while that with non-VEPA therapy was 14.3%. No cases of stage IV showed complete remission, whereas the complete remission rate for cases of stage III was 37.5% for VEPA therapy, but 27.6% for non-VEPA therapy. From these results we concluded that VEPA therapy is more effective for non-Hodgkin's lymphoma, especially large-cell type, than non-VEPA therapy.     

Non-Hodgkin's lymphoma: correlation of cell surface marker phenotype with clinical features and prognosis

The correlation of surface marker phenotype with prognosis was analysed in 64 patients with non-Hodgkin's lymphoma who had been treated in Shikoku Cancer Center Hospital. B-cell lymphomas (21 cases) had significantly better prognosis than T-cell lymphomas (21 cases). The complete remission (CR) rate was 52%, and the 50% survival time was 13 months for T-cell lymphomas. All T-cell lymphoma patients died within 31 months. In B-cell lymphomas, on the other hand, the CR rate was 100%, 50% survival time was 30 months, and there were no cases of relapse in patients who had been in continuous CR for more than 2 years. About 40% of B-cell lymphomas appeared to have the potential for cure.     

Improved prognosis of diffuse histiocytic and undifferentiated lymphoma by use of high dose methotrexate alternating with standard agents (M-BACOD)

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

Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M

One hundred sixty-three patients with advanced non-Hodgkin's lymphoma including adult T cell leukemia/lymphoma (ATL) were treated from 1981 to 1983 with VEPA (vincristine, cyclophosphamide, prednisolone, and doxorubicin) or VEPA-M (VEPA plus methotrexate) in randomized fashion after stratification by surface marker. The complete response (CR) rate and the 4-year survival rate of patients treated with VEPA-M was 62.2% and 36.9%, respectively, while for those treated with VEPA the rates were 51.9% and 26.6, respectively. The difference was not statistically significant, but pretreatment characteristics predictive for response and survival were interesting. Three factors, leukemic change, poor performance status (PS), and T cell marker, were negatively associated with both CR and survival rates, and high-grade pathology was adversely associated with survival rate in a multivariate analysis. These prognostic factors are somewhat different from those in Western lymphomas. This may be reflection of major differences in patients' characteristics between Japanese and Western lymphomas: in this study, there was a high incidence of T cell lymphoma/leukemia (50%) including ATL (33%), leukemic manifestation (34%), poor PS (34%), and a low incidence of follicular lymphoma (9%). The statistically significant three factors for both CR and survival rates were used to construct a model containing eight categories of patients at increasing risk for poor response and shortened survival. These categories were divided into four groups, with respective CR and 4-year survival rates of 91% and 73%, 67% and 35%, 27% and 7%, and 10% and 5%. Ninety-three patients in whom CR was induced by VEPA or VEPA-M therapy were evaluated for prognostic factors predictive for disease-free survival. A shorter period (less than 28 days) required to achieve CR, a clinical diagnosis of ATL, and a lower hemoglobin level were found to affect disease-free survival adversely. These results have important implications for both the design of prospective randomized therapeutic trials and the determination of optimal therapy for individual patients.     

Phase II study of pentostatin in advanced T-cell lymphoid malignancies: update of an M.D. Anderson Cancer Center series

BACKGROUND: The goal of the current study was to assess the toxicity, safety, and efficacy of pentostatin in patients with T-cell lymphoid malignancies. METHODS: Patients were eligible if they had biopsy-proven T-cell lymphoma or leukemia and failure to respond to previous therapy or an expected complete response rate to conventional therapy of < 20%. Pentostatin was administered at an initial dose of 3.75 or 5.0 mg/m(2) by intravenous bolus daily over a consecutive 3-day period every 3 weeks. RESULTS: Forty-two of 44 patients enrolled in the study were evaluable. The median age of the patients was 62 years (range, 38-86 years). Patients received a median of 3 previous therapies (range, 0-10 previous therapies). Of these patients, 32 (76%) had mycosis fungoides/Sézary syndrome and 10 patients (24%) had other T-cell leukemias or lymphomas. The overall response rate was 54.8% (complete remission, 6 patients [14.3%]; partial remission, 17 patients [40.5%]). Durable responses were observed mainly in patients with Sézary syndrome or peripheral T-cell lymphoma. The median follow-up period for surviving patients was 20 months (range, 1-83+ months). The median duration of response was 4.3 months (range, 1-61 months). The most common toxicities were neutropenia, nausea, and CD4 suppression. A transient early "flare" of disease was observed in some responders. CONCLUSIONS: At these doses, pentostatin was reasonably well tolerated and is an effective drug for the treatment of T-cell lymphomas.     

Treatment outcome and pattern of failure in 77 patients with sinonasal natural killer/T-cell or T-cell lymphoma

BACKGROUND: Sinonasal natural killer (NK)/T-cell or T-cell lymphoma behaves quite differently from other lymphomas. The objective of this study was to investigate clinical features, treatment outcomes, and failure patterns in patients with this type of sinonasal lymphoma. METHODS: From September, 1977 to December, 2000, 77 patients with sinonasal NK/T-cell lymphoma or T-cell lymphoma who had received radiotherapy (R/T), chemotherapy (C/T), or both (R/T and C/T) were evaluated retrospectively. RESULTS: Fifty-six patients (73%) had locoregional disease only, and 21 patients (27%) had systemic involvement. Forty-four patients (57%) achieved a complete remission (CR). The 5-year overall survival rate was 36% (median follow-up, 89 months). Achievement of CR was the only prognostic factor for survival in multivariate analysis. Among patients with locoregional disease, the CR rate was 63%, and the 5-year overall survival rate was 42%. Combined R/T and C/T or R/T alone resulted in better survival compared with C/T alone (5-year survival rates, 59%, 50%, and 15%, respectively; P = 0.01). Incidences of locoregional and systemic failure were 43% and 30%, respectively. Outcome was dismal for patients with systemic disease, with a CR rate of 43% and a 5-year survival rate of 25%. Only 2 of 21 patients had sustained remissions. The locoregional and systemic failure rates were 57% and 71%, respectively. CONCLUSIONS: Treatment outcomes were unsatisfactory for patients with locoregional and systemic sinonasal NK/T-cell or T-cell lymphoma. R/T could not control locoregional disease satisfactorily, and C/T was unable to eradicate systemic disease in many patients. High-dose therapy may be worth studying in these patients. New treatments should be investigated to increase remission rates, prevent failure, and improve survival.     

Comparison of CHOP versus VEPA Therapy in Patients with Lymphoma Type of Adult T-cell Leukemia

Forty-six Japanese patients with lymphoma type of adult T-cell leukemia (ATL) were treated with one of the 4-drug combinations, CHOP or VEPA regimen. Fourteen patients were treated with CHOP, while 32 were treated with VEPA. The complete response i(CR) rate and the 5-year survival rate of patients treated with CHOP were 35.7% and 7.1%, respectively, while for those treated with VEPA the rates were 43.8% and 18.7%, respectively. Only two patients treated with CHOP survived for more than 1 year, while the others died within 1 year. On the other hand, 13 patients treated with VEPA survived for more than 1 year. The 32 VEF'A-treated patients were divided into two groups according to the duration of survival: (A) 13 surviving for more than 1 year, and (B) 19 surviving for less than 1 year. They were compared for pretreatment characteristics. The differences between the two groups related to hepatomegaly, the presence of B symptoms, lactic dehydrogenase (LDH) and calcium levels. The results indicate that these factors are important in predicting the response and survival of patients with lymphoma type of ATL.     

Peripheral T-cell lymphoma

Peripheral T-cell lymphoma is the most common type of T-cell lymphoma seen in adults in the United States. Clinical data were reviewed from 134 cases of peripheral T-cell lymphoma diagnosed in three centers. The median age of the patients was 57 years (range, 4-97 years), 59% were male, and 36 patients (27%) had a history of a preceding disorder of the immune system. The tumors were grouped histologically into large cell (43%), mixed large and small cell (40%), and small cell (17%). The stage at diagnosis was I (7%), II (21%), III (22%), and IV (50%). B symptoms were present in 57%. The most frequent sites of extranodal involvement were bone marrow (35%), skin (13%), and lung (11%). Eighty patients were treated with a multiagent chemotherapy regimen with proven curative potential in aggressive non-Hodgkin's lymphomas and the remainder of the patients received less intensive chemotherapy (36 patients), radiotherapy (nine patients), or no treatment (nine patients). Fifty percent of the intensively treated patients achieved complete remission and the actuarial 4-year survival was 45%. However, the 4-year, disease-free survival in patients with Stage IV disease was only 10%. Although peripheral T-cell lymphomas appeared similar in many ways to their B-cell counterparts, disease-free survival by stage was low and patients with Stage IV disease had an especially poor outlook.     

Treatment of low-grade and intermediate-grade lymphoma with intensive combination chemotherapy results in long-term, disease-free survival.

To define the role of intensive combination chemotherapy in the treatment of low-grade or intermediate-grade lymphomas, the authors report results in 49 patients treated with intermediate-dose or high-dose methotrexate, bleomycin, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cytoxan (cyclophosphamide), vincristine, and dexamethasone (m/M-BACOD) with long-term follow-up. The complete response rate was 59% (29 of 49), including 67% (eight of 12) with low-grade and 57% (21 of 37) with intermediate-grade disease. The median survival for the entire group was 81 months. The 29 complete responders had a long median survival of 131 months. Forty-five percent (13 of 29) of the complete responders, 27% of the entire group, continue in remission with a median disease-free survival of 76 months. This includes five of 19 patients with diffuse poorly differentiated lymphoma, a disease generally characterized by early relapse. Twelve patients achieved a partial response and had a shorter median survival of 53 months, whereas nonresponders survived a median of less than 5 months. Late relapse was noted in patients with low-grade and intermediate-grade disease. Age (younger than or older than 60 years) was the only predictor of long-term survival. These data indicate very long disease-free survival can be achieved in low-grade and intermediate-grade lymphomas after attaining a complete remission. Intensive doxorubicin containing chemotherapy can be considered as an option for patients with advanced low-grade lymphoma but can only be proven to be superior to single-agent chemotherapy or no initial therapy by controlled randomized trails.     

原发结外非霍奇金淋巴瘤110例临床分析

目的:探讨原发结外非霍奇金淋巴瘤(PE-NHL)的发病情况、临床特点、诊断及治疗.方法:回顾性分析苏州大学附属第二医院2001年1月～2008年5月收治的PE-NHL 110例.结果:110例PE-NHL占同期收治恶性淋巴瘤患者的60.11%(110/183);原发部位广泛,常见部位依次为胃肠道21.82%(24/110)、Waldeye环10.91%(12/110)、鼻腔和软组织各9.10%(10/110)、纵隔7.27%(8/110)、其他少见部位41.82%(46/110);首发表现以原发器官肿大或肿块为主(77.27%),无特异性;90例患者国际预后指教(IPI)评分:低、中、高危组分别占41.11%、44.44%、14.44%.93例进行免疫分型:B细胞型69.90%,T细胞型30.10%;95例接受治疗,CR 61.05%,PR 16.84%,总有效率77.89%,中位生存时间30个月(2～86个月),5年总生存率27%.24例原发胃肠道非霍奇金淋巴瘤(PGIL),其临床特征与非原发胃肠道组比较无统计学差异,治疗23例,CR 65.21%,PR 17.39%,总有效率82.60%,中位生存时间24个月(2～78个月),5年总生存率30%.结论:本组资料中PE-NHL比例高达60.11%,超过结内淋巴瘤;其首发部位广泛,临床表现多样但无特异性;全面认识本病、遵循合理的诊治模式是提高疗效的关键.     

Short-term weekly chemotherapy followed by high-dose therapy with autologous bone marrow transplantation for lymphoblastic and Burkitt's lymphomas in adult patients

Background: Type and duration of treatment for highly aggressivenon-Hodgkin's lymphoma has been a matter of debate over thepast decade. To determine the therapeutic efficacy of an abbreviatedtreatment regimen, 26 patients with newly-diagnosed highly aggressivelymphomas, 17 of them belonging to the International WorkingFormulation (IWF) group I and 9 with Burkitt's lymphoma (IWFJ), were entered in a study using short-term weekly chemotherapyfollowed by high-dose therapy and autologous bone marrow transplantation.Patients and methods: Besides histology, requirements for entryinto to the study were age between 16 and 60 years, stage Ibulky disease and elevated LDH or stage II to IV disease withor without bulk or elevated LDH, and an absence of HTV infectionor CNS involvement at diagnosis. The treatment plan was 12 weeksof MACOP-B or VACOP-B chemotherapy followed by high dose therapyand autologous bone marrow transplantation in first completeremission. Results: Twenty patients (76%), 16 (62%) of thoseon MACOP-B or VACOP-B, 1 who had received 2 cycles of ProMACE-CytaBOMprior to MACOP-B and 3 after a first salvage reigmen, achievedcomplete remissions. Seventeen patients (65%) were transplantedin first remission, and 15 (58%) after induction treatment withonly MACOP-B or VACOP-B. Reasons for not being given high dosetherapy and autologous bone marrow transplantation (ABMT) werefailure to achieve complete remission in 6 patients, early relapsein 2 and severe pulmonary toxicity associated with chemotherapyin 1. The median time of follow-up was 45 months. At 3 years,the estimated event-free survival was 31% (CI 14%–50%)and the overall survival 48% (CI 25%–67%). There wereno deaths from toxic effects of treatment. Pretreatment factorsassociated with relapse were stage III or IV disease, age over30 years and bone marrow involvement. Logrank analysis showedthat age was the only factor significantly associated with poorevent-free survival. Conclusion: Short-term weekly chemotherapyfollowed by high-dose therapy with the CBV regimen in firstremission is not a highly effective treatment for advanced lymphoblasticand Burkitt's lymphomas. The 30% rate of failure to achievepartial remission after 6 weeks and/or complete response after12 weeks of MACOP-B or VACOP-B treatment, as well as the 42%failure rate to undergo ABMT in first remission, suggest thatmore aggressive chemotherapy should be used in the beginning. lymphoblastic lymphoma, Burkitt's lymphoma, VACOP-B, MACOP-B, ABMT, first remission     

Peripheral/post-thymic T-cell lymphomas: a spectrum of disease. Clinical, pathologic, and immunologic features of 78 cases

The clinical, pathologic, and immunologic features of 78 cases of peripheral/post-thymic T-cell lymphomas are described. These neoplasms were extremely heterogeneous and were classified as small lymphocytic, mixed small and large cell, large cell, lymphoepithelioid cell, angiocentric, and adult T-cell leukemia/lymphoma type. Some cases revealed angioimmunoblastic or Hodgkin's-like features. These neoplasms mainly affected older adults (mean age, 57 years; median age, 60 years). Lymphadenopathy represented the most frequent clinical presentation, although most patients demonstrated both nodal (87%) and extranodal involvement (77%) during the course of disease. Sites of extranodal disease included skin/soft tissue, spleen, lung, liver, bone, gastrointestinal tract, central nervous system, peripheral blood, nasopharynx, and retrovaginal tissue. Splenomegaly at presentation was most frequently observed in lymphoepithelioid cell lymphomas. Angiocentric lymphomas involved lung. A mediastinal presentation was typically observed in young adults and associated with a poor prognosis. Patients with gastrointestinal lymphomas presented with bleeding and/or malabsorption. B symptoms were present in most cases (65%). Hypercalcemia occurred in four patients. Phenotypic studies of T-cell antigens demonstrated the loss of one or more pan-T-cell markers in eight of 47 cases evaluated. Assessment of T-cell subsets revealed a helper/inducer phenotype for nearly all immunoreactive cases. For the overall series, 32 patients died of disease (median survival time, 11.5 mo). There was a statistical difference between the combined groups of small lymphocytic and lymphoepithelioid cell types as compared with mixed and large cell types, with a poorer survival for the latter group. Angiocentric and adult T-cell leukemia/lymphoma were associated with poor survival. This series of T-cell lymphomas further documents the marked heterogeneity of this group of neoplasms as well as the poor prognosis observed for certain histologic types.     

Peripheral T-cell lymphoma. A clinicopathologic study of a morphologically diverse entity

We analyzed the clinicopathologic features of 13 patients with immunologically confirmed peripheral T-cell lymphoma. The lymphomas were classified into poorly differentiated lymphocytic, mixed cell, and large cell types. Marked morphologic heterogeneity was noted within the mixed cell and large cell categories, and the various subtypes are described. Twelve of the 13 patients received multiagent chemotherapy. Only three of the nine patients with poorly differentiated or mixed cell lymphomas achieved a complete remission, and the median survival for this group was 11 months. In contrast, all three of the treated patients with large cell lymphomas achieved a complete remission, two of whom are alive without disease (14 and 29 months, respectively). Classification of peripheral T-cell lymphomas into lymphocytic, mixed cell, and large cell types, as well as further subclassification within the heterogeneous groups, is suggested so that pathologic features of prognostic significance can be identified.     

Clinical significance of immunophenotype in diffuse aggressive non-Hodgkin's lymphoma

We performed a prospective study of the clinical significance of immunophenotype in 110 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by oncologists in the Nebraska Lymphoma Study Group between October 1982 and May 1986. All patients were immunophenotyped from biopsies performed before therapy was administered. The patients were treated with a uniform protocol of radiotherapy for minimal nonbulky, stage I or II disease (seven patients) or a single, six-drug chemotherapy regimen cyclophosphamide, doxorubicin, procarbazine, bleomycin, vincristine, and prednisone (CAP-BOP) in patients with more extensive disease (103 patients). Ninety-one patients (83%) had B-cell lymphoma and 19 patients (17%) had T-cell lymphoma. The histologic diagnosis of diffuse mixed-cell lymphoma was significantly associated with T-cell immunophenotype (45% v 5%; P less than .001), and the diagnosis of diffuse large-cell lymphoma was significantly associated with B-cell immunophenotype (40% v 5%; P = .006). However, no significant difference in frequency of prognostic variables such as age, stage, systemic symptoms, tumor bulk, serum lactic dehydrogenase, or performance status was found between the B-cell and T-cell groups. Patients with B-cell NHL had a slightly higher complete remission rate (74% v 53%; P = NS), similar durability of complete remission (75% v 70% at 3 years; P = NS), and a slightly but not significantly better overall survival (50% v 41% at 3 years; P = NS). The slight advantage in response rate and survival for B-cell patients was related to a very poor outcome for patients with stage IV T-cell NHL. For patients with stage I to III disease, neither the complete remission rate (B-cell, 82% v T-cell, 91%; P = NS) nor overall survival (3-year survival for B cell, 58% v T cell, 73%; P = NS) were significantly different. However, with stage IV disease B-cell patients fared far better than those with T-cell NHL for both complete remission rate (67% v 0%; P = .002) and overall survival (3-year survival, 44% v 0%; P = .002). Immunophenotyping intermediate- and high-grade NHL allowed identification of a subgroup of patients who had a very poor prognosis with this treatment approach and for whom alternate therapy might be considered.     

Major prognostic factors of adult patients with advanced T-cell lymphoma/leukemia

Eighty-one adult patients with advanced T-cell lymphoma/leukemia including 54 with adult T-cell leukemia/lymphoma (ATL), who were treated between 1981 and 1983 with vincristine, cyclophosphamide, prednisolone, and doxorubicin (VEPA) or VEPA plus methotrexate (VEPA-M) in randomized fashion, were evaluated for pretreatment characteristics. The overall complete response (CR) and the 4-year survival rates were 39.5% and 19.4%, respectively, and 69% of 32 CR patients had relapses, indicating the need for development of new effective regimens for the disease. In a multiple logistic regression analysis, only three factors, leukemic manifestation, poor performance status (PS), and a high lactate dehydrogenase (LDH) level, were significantly associated with the poor response rate. In a Cox proportional hazards model analysis, shortened survival was again significantly associated with poor PS and a high LDH level, but not with a clinical diagnosis of ATL. The two factors, PS and LDH level, that were found to be significantly associated with both CR and survival rates, were used to construct a model containing six categories of patients at increasing risk for poor response and shortened survival. These categories divided the patients into three groups with respective CR and 4-year survival rates of 75% and 53% for low-risk, 45% and 15% for moderate-risk, and 15% and 0% for high-risk. The results indicate that PS and LDH levels were the most important in predicting the response and survival of an adult patient with advanced T-cell lymphoma/leukemia. The prognosis of patients with usual peripheral T-cell lymphoma, excluding ATL, was comparable with that of advanced B-cell lymphoma. These results have important implications for the design of new prospective therapeutic trials.     

High-dose therapy and autologous stem cell transplantation in Korean patients with aggressive T/NK-cell lymphoma

The proportion of aggressive T/NK-cell lymphoma in Korea is larger than in the West, and it shows a lower response to conventional chemotherapy and poorer survival than diffuse large B-cell lymphoma. This study was undertaken to evaluate the response rate and survival and to document the prognostic factors in patients with T/NK-cell lymphoma who have undergone high-dose therapy (HDT). Eligibility for the study was a mature T/NK-cell lymphoma with initially poor risk (as high or high intermediate risk on age-adjusted International Prognostic Index) or relapsed cases. Twenty-eight patients from 6 centers were reviewed retrospectively. The M : F ratio was 20:8, and median age was 36 years (range 16--60 years). Twelve patients had unspecified peripheral T-cell lymphomas, 7 anaplastic large-cell lymphomas, 6 nasal T/NK-cell lymphomas, and 3 angioimmunoblastic T-cell lymphomas. Disease status at transplant were initially poor risk in 15, chemosensitive relapse in 8 and chemo-resistant relapse in 5 patients, respectively. A complete response (CR) after HDT comprised 20 patients, including 16 with continued CR. Absolute neutrophil count ( > 500/microl) recovered at a median 11 days after autologous stem cell transplantation in 26 patients. Two therapy-related mortalities occurred. Estimated 3-year event-free survival and overall survival (OS) (+/- SE) were 24+/- 9 and 42+/- 10 months, respectively. Only CR status after HDT influenced OS (P=0.000). Therefore, an initial approach with effective induction and HDT may result in a better outcome in T/NK-cell lymphoma.     

Peripheral T-cell lymphoma: a clinicopathologic study of 42 cases

Clinical and histopathologic material from 42 patients with peripheral T-cell lymphoma (PTCL) was reviewed. The median age was 63.5 years (range, 11-97 years). The male:female ratio was 2.8:1. Prior immune or lymphoproliferative diseases occurred in 36% of the patients. PTCL was advanced at presentation with B symptoms (67%), generalized adenopathy (69%), and stage III/IV disease (79%). Suspected lung or pleural involvement (21%), hepatomegaly (29%), and splenomegaly (43%) were common; marrow involvement was documented in 37% of the patients at presentation and in 51% of patients during the illness. Hypercalcemia and eosinophilia occurred in 19% and 29% of patients, respectively. Among patients receiving combination chemotherapy (BCOP, CHOP, BACOP, COMLA), eight (24%) of 33 achieved a complete remission and only four (12%) of 33 had a sustained complete remission. The median survival for PTCL was 11 months. Because of the poor response to standard therapy, clinical trials should identify cases of PTCL and evaluate newer regimens in this subset of aggressive lymphoma.