British National Lymphoma Investigation Research Articles

Phase 2 Study of Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma

Combined modality therapy, consisting of chemotherapy (ChT) followed by radiation therapy (RT), is an established treatment paradigm for diffuse large B-cell lymphoma (DLBCL). A British National Lymphoma Investigation randomized trial demonstrated no difference in clinical outcomes, including local control, between 30 Gy and 40-45 Gy. Few patients in this study received rituximab or had PET-CT imaging to assessment ChT response. The hypothesis of this phase II study was that more effective systemic therapy (incorporation of rituximab) and optimal post-ChT response assessment (PET-CT), will allow the RT dose to be reduced from 30 Gy to 20 Gy while maintaining high rates of local control. Eligibility for this institutional review board-approved, phase II prospective trial required histological documentation of DLBCL, receipt of ≥ 4 cycles of a rituximab/anthracycline-containing combination ChT regimen, and a negative post-chemotherapy PET-CT. Deauville criteria were adopted in 2013 with a negative scan defined as scores 1-3 (prior patients were scored retrospectively). Primary CNS lymphoma was excluded. Patients with stage I/II disease were treated comprehensively to all sites of original involvement; treatment fields for those with stage III/IV disease were individualized. RT field design followed principles of involved-site radiation therapy (ISRT). RT dose was 19.8-20 Gy in 1.8-2 Gy fractions. Primary endpoint: 5-year local recurrence-free survival. Secondary endpoints: 5-year progression-free survival (PFS) and overall survival (OS). PFS defined as time from initiation of RT to progression due to lymphoma or death, whichever occurred first and censored at last follow-up date. Kaplan Meier estimates were used to estimate PFS and OS. From 2010-2015, 62 patients were enrolled (34 women, 28 men; median age: 58 years [range, 24-86 years]). Stage distribution: I (24, 39%), II (25, 40%), III (4, 6%), IV (9, 15%). Median largest tumor mass at diagnosis: 5.7 cm (range, 1-20). Bulky disease (defined as ≥7.5 cm or ≥ 10 cm) present in 23 (40%) and 16 (28%) of patients, respectively. ChT: R-CHOP in 58 (94%) and R-EPOCH in 4 (6%). Number of ChT cycles: 4 (n = 25, 40%); 5 (n = 2, 3%); and 6 (n = 35, 57%). Post-ChT Deauville scores: 1 (23, 37%), 2 (23, 37%), 3 (15, 24%), and 4 (1, 2%). Comprehensive RT administered to 4/4 patients with stage III and 6/9 patients with stage IV disease- 3 patient with stage IV disease received RT to only select sites. With a median follow-up of 34 months (range, 1-73), there were no local failures with LRFS of 100%. Systemic lymphoma progression developed in 4 patients with stage I/II disease and 1 with stage IV disease. There were 3 deaths (DLBCL, glioblastoma, unknown). PFS at 3 and 5 years: 92% (95% CI: 86-100%) and 78% (95% CI: 63-97%). OS at 3 and 5 years: 100% and 91% (95% CI: 79-100%). With more effective systemic therapy (R-CHOP) and more refined ChT response assessment (PET-CT), the dose of RT in combined modality treatment programs may be able to be further reduced to 20 Gy.

Improving Survival of Patients With Hodgkin Lymphoma Over 4 Decades: Experience of the British National Lymphoma Investigation (BNLI) With 6834 Patients.

The management of Hodgkin lymphoma (HL) has changed markedly over the last 50 years. This is due to the expanding understanding about the biology of the disease, the development of increasingly efficacious multimodal treatment, and the recognition of how to reduce late effects. The British National Lymphoma Investigation (BNLI) was formed in the 1970s to coordinate UK research in the diagnosis and treatment of lymphoma. We describe the improvement in trial patient survival over 4 decades. This analysis is of data on 6834 patients with a de novo diagnosis of HL registered onto studies with BNLI oversight from January 1, 1970, to December 31, 2009. Patients were subdivided in 4 groups according to their decade of registration; 1970s, 1980s, 1990s, and 2000s. Because of the lengthy data collection period, there is a difference in duration of follow-up between decade groups, with median follow-up in the 1970s group of 28.2 years, 18.0 years in the 1980s group, 9.4 years in the 1990s group, and 5.4 years in the 2000s group. Comparison between data in all 4 groups is not possible beyond 13.4 years (maximum duration of follow-up in the 2000s group), and so a cutoff has been applied at 14 years. Data on overall survival, cause of death, primary treatment modality, and incidence of secondary malignancy were collected. Clear and statistically significant improvements in survival curves between the decades were present, with 10-year overall survival increasing from 62.4% in the 1970s to 89.6% in the 2000s. There was a suggestion that second malignancy and cardiac-related deaths have been reducing over time, but longer follow-up is needed for the later decades to confirm this trend. Results support existing registry data demonstrating that survival for HL has improved over the 4 decades analyzed. This data set is robust and validated, and it adds valuable understanding to the reasons behind the survival curves, which are a balance between efficacious therapies and decreased death related to cardiac conditions and second malignancies.

Fractionated 90Y-Ibritumomab Tiuxetan Radioimmunotherapy As an Initial Therapy of Follicular Lymphoma: An International Phase II Study in Patients Requiring Treatment According to GELF/BNLI Criteria

We report an international, multicenter phase II trial to evaluate the efficacy and toxicity of fractionated (90)Y-ibritumomab tiuxetan ((90)Y-IT) as initial therapy of follicular lymphoma (FL). A total of 74 patients, with a median age of 61 years (range, 28 to 80 years), were recruited requiring initial therapy by Groupe d'Etude des Lymphomes Folliculaires (GELF)/British National Lymphoma Investigation (BNLI) criteria. Among them, 78% had stage III-IV disease, 32% intermediate, and 44% high-risk (according to FL International Prognostic Index). Treatment consisted of two doses of (90)Y-IT (11.1 MBq/kg) administered 8 to 12 weeks apart. Patients with more than 20% lymphoma infiltration of bone marrow (BM) received one infusion per week for 4 consecutive weeks of rituximab (375 mg/m(2)) and proceeded to fractionated radioimmunotherapy (RIT) only if a repeat BM biopsy demonstrated clearing of lymphoma to less than 20% involvement. The primary end point was end of treatment response of the intention-to-treat population. Secondary objectives were safety and progression-free survival (PFS). Initial overall response rate (ORR) was 94.4% (68 of 72 patients) with combined complete response (CR/CRu) of 58.3% (42 of 72 patients). Nine patients subsequently improved response making an ORR of 95.8% (69 of 72 patients) and CR/CRu of 69.4% (50 of 72 patients). At a median follow-up of 3.1 years (range, 0.2 to 5.2 years) estimated 3-year PFS is 58%, treatment-free survival 66%, and overall survival 95%. Median PFS is 40.2 months. Thirty patients have experienced disease progression and 24 have required further treatment. The treatment was well tolerated with few (2.8%) grade 3 or 4 infectious episodes or adverse events and manageable hematologic toxicity. Fractionated RIT using (90)Y-IT is an effective initial treatment for advanced-stage FL in patients with higher tumor burden requiring treatment.

Guidelines for the investigation and management of mantle cell lymphoma.

The guideline group was selected to be representative of UK-based medical experts and patients representatives. Ovid MEDLINE, EMBASE and NCBI Pubmed were searched systematically for publications in English from 1980 to 2011 using the MeSH subheading 'lymphoma, mantle cell' and 'lymphoma, mantle cell' as a keyword, as well as all subheadings. In addition, all references to mantle cell lymphoma in the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissue (Swerdlow et al, 2008) and the British Committee for Standards in Haematology (BCSH) Guideline: Best Practice in Lymphoma Diagnosis and Reporting (Parker et al, 2010) have been included. The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemato-oncology Task Force of the BCSH. The guideline was then reviewed by a sounding board of approximately 50 UK haematologists, the BCSH and the British Society for Haematology Committee and comments incorporated where appropriate. The 'GRADE' system was used to quote levels and grades of evidence, details of which can be found in Appendix I. The objective of this guideline is to provide healthcare professionals with clear guidance on the investigation and management of patients with mantle cell lymphoma. The guidance may not be appropriate to patients with other lymphoma sub-types and in all cases individual patient circumstances may dictate an alternative approach.

Inflammatory (B) symptoms are independent predictors of myelosuppression from chemotherapy in Non-Hodgkin Lymphoma (NHL) patients – analysis of data from a British National Lymphoma Investigation phase III trial comparing CHOP to PMitCEBO

BackgroundToxicity from chemotherapy is highly variable, unpredictable and results in substantial morbidity and increased healthcare costs. New predictors of toxicity are required to improve the safety and efficacy of chemotherapy. Inflammatory or B symptoms in lymphoma are associated with elevated plasma inflammatory markers and predict worse treatment response and survival. Recent data suggest that systemic inflammation results in reduced hepatic drug metabolism and increased toxicity from chemotherapy. We investigated whether B symptoms were associated with greater toxicity in patients treated for non-Hodgkin lymphoma (NHL).MethodsThe British National Lymphoma Investigation compared two chemotherapy regimens in older patients with aggressive NHL. Approximately 50% of patients had B symptoms. Demographic and toxicity data on 664 patients were analysed to identify predictors of toxicity by multivariate analysis, with particular reference to B symptoms.ResultsUsing univariate analyses, severe (grades 3–4) leucopenia, anaemia, thrombocytopenia, nausea and vomiting and diarrhoea occurred more frequently in patients with B symptoms. The associations between B symptoms and severe leucopenia (OR 1.7, p = 0.005) and anaemia (OR 2.3, p = 0.025) persisted after adjustment for other prognostic factors in multivariate analyses. The use of granulocyte colony stimulating factor reduced neutropenia in patients with both A and B symptoms.ConclusionFor the first time and in a large NHL cohort we have shown that inflammatory symptoms are independent predictors for myelosuppression from chemotherapy. These data will enable improved prognostication for toxicity and provide individualisation of therapy in NHL and other tumours. These findings also create the potential for strategies used prior to chemotherapy aimed at reducing systemic inflammation in order to improve drug metabolism and reduce treatment-related toxicity.Trial registration numberISRCTN98741793

Risk of Second Malignancy After Non-Hodgkin's Lymphoma: A British Cohort Study

To assess long-term site-specific risks of second malignancy following non-Hodgkin's lymphoma (NHL) in relation to treatment and demographic factors. A cohort of 2,456 patients with NHL who were first treated from 1973 to 2000 and were younger than 60 years from centers in the British National Lymphoma Investigation were observed, and occurrences of second malignancy was compared with expectations based on general population cancer rates in England and Wales. In total, 123 second malignancies occurred. Relative risks (RRs) were significantly elevated for all malignancies combined (RR = 1.3; 95% CI, 1.1 to 1.6) and for leukemia (RR = 8.8; 95% CI, 5.1 to 14.1) and lung cancer (RR = 1.6; 95% CI, 1.1 to 2.3). RRs of malignancy overall diminished significantly with increasing age at first treatment. Leukemia risk was significantly increased after chemotherapy (RR = 10.5; 95% CI, 5.0 to 19.3) and mixed-modality treatment (RR = 13.0; 95% CI, 5.2 to 26.7). Relative risks of lung (RR = 1.9; 95% CI, 1.1 to 3.1) and colorectal (RR = 2.1; 95% CI, 1.1 to 3.6) cancers were significantly raised following chemotherapy. NHL patients are at elevated risk of developing second malignancy, particularly leukemia and lung cancer. The relative risk is greater with patients who are younger at first treatment. Chemotherapy predisposes patients toan increased risk of leukemia, and possibly lung and colorectal cancers. The role of specific drug treatments in the etiology of solid cancers after NHL deserves further investigation.

Trials in Advanced Hodgkin's Disease: More than 30 Years Experience of the British National Lymphoma Investigation

Hodgkin's disease demonstrates an exquisite sensitivity to chemotherapy and radiation therapy. This necessitates investigation of modes of delivering these modalities in the best possible fashion to improve outcomes. The British National Lymphoma Investigation (BNLI) has conducted randomized trials in advanced Hodgkin's disease for > 30 years. The results of BNLI studies have demonstrated that MOPP (mechlorethamine/vincristine/procarbazine/prednisone) chemotherapy is superior to MOP (mechlorethamine/vincristine/procarbazine) chemotherapy; that there are no significant differences between MOPP and B-MOPP (MOPP plus bleomycin); that there is no significant benefit from maintenance therapy with lomustine/vinblastine/bleomycin; that LOPP (chlorambucil/vincristine/procarbazine/prednisone) is as effective as MOPP and has less acute toxicity; that alternating therapy with LOPP and EVAP (etoposide/vinblastine/doxorubicin/prednisolone) is superior to EVAP alone or hybrid LOPP and EVA (etoposide/vinblastine/doxorubicin); that alternating therapy with ChlVPP (a substitute for MOPP) and prednisolone/doxorubicin/bleomycin/vincristine/etoposide regimens is superior to the latter regimen alone; that the Stanford V regimen (doxorubicin/vinblastine/mechlorethamine/vincristine/bleomycin/etoposide/prednisone) combined with disciplined radiation therapy is safe and effective; that hybrid therapy with ChlVPP and EVA and alternating therapy with ChlVPP and prednisolone/ doxorubicin/bleomycin/vincristine/etoposide are as effective as ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) alone; and that there is no additional benefit from total nodal irradiation or combined-modality therapy compared with MOPP; and that treatment with high-dose BEAM (carmustine/etoposide/cytarabine/melphalan) and autologous bone marrow transplantation is superior to mini- BEAM (lower-dose BEAM not requiring bone marrow rescue) for poor-risk relapsed and refractory disease.

Long Term Outcome in Adolescents with Hodgkin's Lymphoma: Poor Results using Regimens Designed for Adults

It is unclear whether the outcome in adolescents with Hodgkin's lymphoma is as good as that in children and there are no prospective randomized trials comparing regimes used in children and adults in this setting. We have therefore performed an analysis of 210 adolescent patients diagnosed with Hodgkin's lymphoma between 1970-1997 and registered on the database held by the British National Lymphoma Investigation. Patients were treated according to adult regimens current at the time of their diagnosis. The complete response rate recorded in 209 patients was 76%. This was highly dependent on disease stage being 95% in patients with localized disease but 63% in those with advanced disease. The 5 year event free survival for the whole cohort was 50% falling to 41% at 20 years with overall survival of 81% falling to 68% at 5 and 20 years respectively. There is no significant difference in the 3 decades pertaining to this analysis. Of the 62 deaths in this cohort, 70% were due to Hodgkin's lymphoma but of the 13 deaths occurring beyond 10 years, only 3 were due to Hodgkin's lymphoma, the reminder being attributable to the late effects of therapy. Results from paediatric groups have been much more encouraging than those presented from this cohort. It seems the use of risk-adjusted combined modality therapy with minimization of radiation fields and doses and reduction of anthracycline and alkylator exposure has been successful in children and should be used in adolescents.

Long-term follow-up of patients treated with radiotherapy alone for early-stage histologically aggressive non-Hodgkin's lymphoma.

Historically localised aggressive non-Hodgkin's lymphoma (NHL) has been treated with involved field radiotherapy (RT), chemotherapy, or a combination of both modalities. The current weight of evidence supports a preference for combined modality treatment (CMT). Increased patient age at diagnosis is well recognised as a poor prognostic indicator in NHL, but despite this some perceive CMT as too toxic for use in the elderly. As a result, some older patients continue to be offered RT alone. Here, we present long-term follow-up of 377 adults of all ages treated with RT alone for early-stage diffuse large-cell lymphoma on British National Lymphoma Investigation trials between 1974 and 1997. 10-year cause-specific survival in patients older than 60 years was poor and significantly inferior to that in younger patients (47 and 75% respectively; P<0.001). There is growing evidence that short-course chemotherapy, with or without RT, is superior to RT alone in early-stage aggressive NHL, in elderly as well as in younger patients. Increased age alone should not exclude patients from systemic treatment for early-stage aggressive NHL.

Risk-adjusted prognostic models for Hodgkin's disease (HD) and grade II non-Hodgkin's lymphoma (NHL II): validation on 6728 British National Lymphoma Investigation patients.

Using significant factors from multivariate analyses, based on 20 putative markers from a consecutive series of 1198 Sheffield Lymphoma Group patients, risk-adjusted prognostic models had been previously derived for Hodgkin's disease (HD) (using age, albumin and lymphocyte count) and non-Hodgkin's lymphoma (NHL) grade II (based on albumin, age, erythrocyte sedimentation rate, lactate dehydrogenase and stage). Data from 6728 patients on the British National Lymphoma Investigation database were used for validation: thus the models were applied to 4411 patients with HD and 2317 patients with NHL grade II. Survival curves derived from these validation groups confirmed our risk models.

British National Lymphoma Investigation: Pilot Studies of Neoadjuvant Chemotherapy in Clinical Stage Ia and IIa Hodgkin's Disease

In order to improve treatment in early Stage IA and IIA Hodgkin's disease, the British National Lymphoma Investigation (BNLI) has evaluated two neoadjuvant chemotherapy regimens with involved field radiotherapy. This article reports the results of the methotrexate, vinblastine and prednisolone (MVP) study in 39 patients and updates the previous report on vinblastine, bleomycin and methotrexate (VBM) in 30 patients. Both studies recruited clinical Stage IA or IIA Hodgkin's disease patients with intermediate risk of relapse into a prospective multicentre Phase II study. They received two cycles of chemotherapy followed by involved field radiotherapy and then four further cycles of chemotherapy. For MVP the 5-year survival is 97% and for VBM it is 93%. The 5-year event-free survival rates are 71% and 87% respectively.The acute pulmonary and haematological toxicity occurring with VBM was not acceptable and therefore the MVP study was performed. There was less toxicity with this regimen although modest acute pulmonary toxicity was still observed. However, in view of the length of treatment with MVP (9 months) and the excellent results reported by the Manchester group, future efforts of the BNLI are to be directed towards a new short course chemotherapy regimen, VAPEC-B (vincristine, doxorubicin, prednisolone, etoposide, cyclophosphamide and bleomycin).

British National Lymphoma Investigation: Pilot Studies of Neoadjuvant Chemotherapy in Clinical Stage Ia and IIa Hodgkin’s Disease

British National Lymphoma Investigation: Pilot Studies of Neoadjuvant Chemotherapy in Clinical Stage Ia and IIa Hodgkin’s Disease

Pathologic and clinical features of 77 Hodgkin's lymphoma patients treated in a lymphoma protocol (LNH87): a GELA study.

Between 1987 and 1993, 77 of 2855 lymphomas included in the LNH87 protocol of the GELA as non-Hodgkin lymphoma (NHL) and reviewed by a panel of pathologists had a diagnosis changed to Hodgkin lymphoma (HL). Some of these lymphomas had been initially interpreted as anaplastic large-cell lymphoma Hodgkin-like (ALCL-HL subtype). The purpose of this study was to analyze the histologic pitfalls initially encountered, to define more clearly the diagnostic criteria of lymphomas placed in the gray zone around HL, and to follow the survival of these 77 patients affected with HL and initially treated with NHL regimens. The 77 cases of HL were reviewed by three hematopathologists and immunostained with a large panel of antibodies, including CD30, CD15, CD3, CD20, CD45, CD43, LMP-1, EMA, BNH-9, TiA1, and ALK1. Each case was classified according to the Lukes-Rye system and the British National Lymphoma Investigation (BNLI) grading. The initial clinical presentation of patients was analyzed, and the overall and event-free survival rates of the 77 patients were estimated. Among the 77 HLs, 46 were misinterpreted as NHL by primary individual pathologists (12 as ALCL, 8 as ALCL-HL, 12 as peripheral T-cell lymphoma (PTCL), 6 as B-cell lymphoma, and 8 as unclassifiable NHL). The other 31 cases had been first considered by the panel as consistent with ALCL-HL (n = 18) or with PTCL (n = 13) and were changed later in view of an immunophenotype concordant with HL. Fifty-five percent of the patients completed the full NHL treatment. The 5-year event-free and overall survival rates were 54% and 77%, respectively. The current results indicate that lymphomas initially called ALCL-HL should not be regarded as a variant of ALCL, but as HL. The clinical consequences of misdiagnoses seem to be a lower event-free survival rate compared with that of classical HL, probably because of more relapses of initially inappropriately treated HL.

Long-term survival in Hodgkin's disease patients: a comparison of relative survival in patients in trials and those recorded in population-based cancer registries

The prognosis of Hodgkin's disease (HD) has improved during the last 30 years. This study was planned to analyse long-term survival of HD patients and to compare survival rates estimated from clinical trials and population-based data. Individual data were analysed on 2755 adult HD patients entering randomised clinical trials of the British National Lymphoma Investigation (BNLI) between 1970 and 1987, and 5064 patients with HD incident 1978–1984 recorded in the UK population-based cancer registries participating in the EUROCARE study. Relative survival of Hodgkin's disease patients allowing for mortality expected from general population rates was analysed by a proportional hazards regression model including covariates. Although relative mortality decreased with longer follow-up, it was still significantly positive at 9–10 years after diagnosis in both the clinical trials and the population-based data sets. Relative mortality was worse for late stage than for early stage patients even at 10–15 years after first treatment (BNLI data). Whereas 10-year relative survival was identical in trials and population-based patients at ages under 45 years (>69%), it was much higher in BNLI older patients than in the population-based patients. In the older age group (65–74 years) the BNLI patients had 39% relative survival whilst for the population-based patients it was only 27%. Generalisation of clinical trials results to the general population must be done with caution, especially for older patients.

Secondary Leukaemia and Myelodysplasia after Autografting for Lymphoma: Is the Transplant to Blame?

Haemopoietic stem cell autografting is becoming a standard part of the therapeutic repertoire for salvage of relapsed lymphoma patients. Over the last five years or so a number of studies have identified that such patients are at high risk of developing secondary acute myeloid leukaemia (AML) or myelodysplastic syndromes (MDS). The actuarial risks have been estimated to be LIP to 18% in some series. More recently, studies from Prance and the EBMT suggest that in Registries containing large numbers of transplanted patients the risks arc lower and arc or the order of 3-5% at five years. Cytogenetic examination of bone marrow cells taken pre-transplant may also show identical abnormalities to those found in the leukaemic clone after transplant indicating that in many instances the stem cell damage was caused by prior treatment. In addition, a report from the British National Lymphoma Investigation has identified that post-transplant MDS/AML was related Lo the total quantity of treatment received, with mustine being identified as a particular culprit. It thus seems probable that the additional stem cell insult offered by the transplant may be small although a factor which may increase the risk is the use of total body irradiation.

A Randomised British National Lymphoma Investigation trial of CHOP vs. a weekly multi-agent regimen (PACEBOM) in patients with histologically aggressive non-Hodgkin's lymphoma

Between 1987 and 1991, the British National Lymphoma Investigation randomized 459 patients with non-Hodgkin's lymphoma with a large-cell component to either CHOP or the PACEBOM regimen. Four hundred fifty-nine eligible patients were included in this trial, four hundred one with diffuse large-cell lymphoma and fifty-eight with diffuse mixed-cell lymphoma according to the Working Formulation. Two hundred twenty-six patients were randomized to receive CHOP and two hundred thirty-three to receive PACEBOM. The two arms of the trial were well balanced for all potential prognostic factors. The complete remission rate with PACEBOM was 64% and with CHOP 57% (NS). At eight years, the actuarial cause specific survival (CSS) in the PACEBOM arm is 59% compared to 49% in the CHOP arm (P = 0.09). Patients < 50 years of age fared significantly better in the PACEBOM arm both for CSS and overall survival (P = 0.002) and the CSS was also significantly improved in stage IV disease (P = 0.02). The mature data from this trial suggest that an etoposide-containing multi-agent weekly regimen can be superior to CHOP.

High-dose therapy for Hodgkin's disease.

High-dose therapy for Hodgkin's disease.

The clinical outcome of 65 cases of mantle cell lymphoma initially treated with non-intensive therapy by the British National Lymphoma Investigation Group.

Mantle cell lymphoma (MCL) was first described as a distinct biological entity on the basis of its association with the t(11;14)(q13;q32) resulting in over-expression of the cyclin D1 gene. Recognition of the morphological, immunophenotypic and clinical characteristics of MCL has enabled the accurate diagnosis of this entity and appreciation of its poor prognosis. Most published series of patients with MCL have used anthracycline-containing regimens. In contrast the British National Lymphoma Investigation (BNLI) group have treated 65 patients with MCL with non-intensive 'low-grade lymphoma' therapy. The median overall survival of 57 months and progression-free survival of 24 months compares favourably with the more intensively treated series. Although the disease was generally more aggressive than other low-grade lymphomas, some patients were asymptomatic and had indolent disease. When compared to 1853 patients with non-MCL low-grade lymphomas entered on the BNLI database, patients were found on average to be older (P=0.02), to have more extranodal disease (P<0.00001), and a higher proportion to have a raised ESR (P=0.02) and a low serum albumin (P=0.002). Multivariate analysis of significant prognostic markers in all BNLI low-grade lymphomas failed to identify MCL as an independent prognostic factor.

1186 - Alternating ChlVPP/PAB1OE is better than PAB1OE alone as initial chemotherapy for advanced Hodgkin's disease (HD): First results of a British National Lymphoma investigation (BNLI)/Central Lymphoma Group (CLG) study

1186 - Alternating ChlVPP/PAB1OE is better than PAB1OE alone as initial chemotherapy for advanced Hodgkin's disease (HD): First results of a British National Lymphoma investigation (BNLI)/Central Lymphoma Group (CLG) study

Disappearance of prognostic significance of histopathological grading of nodular sclerosing Hodgkin's disease for unselected patients, 1972-92.

The importance of the subclassification of nodular sclerosing Hodgkin's disease (NSHD) according to the British National Lymphoma Investigation Group (BNLI) criteria, which had an independent prognostic value for 90 unselected patients diagnosed in our region in the period 1972-83, is still equivocal. Because survival of patients with Hodgkin's disease improved in our region during the period 1972-92 and because treatment may modify prognostic factors, we re-evaluated the prognostic value of NSHD subclassification up to 1993. A registry-based study was performed with data on all 345 Hodgkin patients diagnosed in the period 1972-92. Available histology was reviewed. The prognostic value of nodular sclerosis (NS) grading was evaluated for two periods, 1972-80 and 1981-92, designated as the seventies and the eighties, respectively. NSHD was diagnosed in 57% (n = 195) of all registered cases of Hodgkin's disease, 17 of which could not be evaluated. NS stage I (NSI; 73%) and NS stage II (NSII; 27%) patients exhibited the same distribution of stage during both periods; NSII patients were older than NSI patients in the seventies. NSII patients presented with an elevated ESR and B symptoms more frequently during the eighties and subsequently received combined modality therapy more often. The crude 5-year survival rate for grade I v grade II NSHD was 85% v 38% (P < 0.05) for the seventies and 84% v 83% for the eighties. Subclassification of NSHD was not an independent prognostic factor after adjustment for age, stage, gender, B symptoms and ESR, though it remained of independent prognostic value when ESR was left out of the Cox model. The most important factors adversely influencing survival were advanced age, advanced stage and male gender. The independent prognostic value of the subclassification of NSHD has disappeared, as reflected by the clearly improved survival of NSII patients, probably due to more intensive treatment in the eighties, whereas survival of NSI patients did not changes.