Up-front rituximab maintenance improves outcome in patients with follicular lymphoma: a collaborative Nordic study.

The introduction of the anti-CD20 antibody rituximab in combination with chemotherapy (R-chemo) has improved the prognosis of patients with follicular lymphoma (FL). During the last decade, the addition of a maintenance treatment with rituximab (MR) after R-chemo has been tested with the hope of further improving the outcome of these patients. Using 2 independent population-based cohorts, we investigated the effect of up-front MR on time related end points as well as the risk of histological transformation (HT). FL patients were included if they: (1) completed first-line induction treatment with R-chemo, (2) were alive after induction treatment and eligible for MR, and (3) had no evidence of HT at this time point. The training cohort consisted of 733 Danish patients of whom 364 were consolidated with MR; 369 were not. Patients receiving MR more often had advanced clinical stage (90% vs 78%), high Follicular Lymphoma International Prognostic Index (FLIPI) score (64% vs 55%), and bone marrow infiltration (49% vs 40%). Those consolidated with MR had an improved 5-year overall survival (OS; 89% vs 81%; P = .001) and progression-free survival (PFS; 72% vs 60%; P < .001). In the training cohort, MR was associated with a reduction of HT risk (P = .049). Analyses of an independent validation cohort of 190 Finnish patients confirmed the favorable impact of MR on 5-year OS (89% vs 81%; P = .046) and PFS (70% vs 57%; P = .005) but did not find a reduced risk of HT. The present population-based data suggest that the outcome of patients with FL has improved after consolidation of R-chemo with MR.

Outcome determinants for transformed indolent lymphomas treated with or without autologous stem-cell transplantation.

BACKGROUND: Transformation of indolent lymphomas (IL) to an aggressive histology (TIL) often results in a rapid clinical course, treatment refractoriness and shortened survival. Although rituximab-containing regimens (R-chemo) have become standard of care in CD20-positive TIL, the role of autologous stem-cell transplantation (ASCT) is still debated. The purpose of this study was to determine whether the outcome of TIL patients improved if they, at transformation, also received ASCT. Furthermore, we investigated the outcome of cases with histologically low- and high-grade components diagnosed either simultaneously or after a period of overt indolent disease. We also analyzed, whether prior rituximab treatment during the indolent course of the disease affected outcome after transformation. PATIENTS AND METHODS: Eighty-five patients (≤68 years) with histologically confirmed TIL were included. Five-year overall (OS) and progression-free survival (PFS) were calculated. Selected parameters were tested in a multivariate analysis. All analyses were conducted on three cohorts: (i) whole cohort (all TIL), (ii) patients with co-existing evidence of both indolent and aggressive histology at diagnosis (Composite/discordant TIL) and (iii) patients transformed after prolonged prior indolent disease (sequential TIL). RESULTS: Fifty-four patients (64%) received ASCT consolidation and 31 (36%) did not. Within the 'all TIL' cohort, the 5-year OS and PFS for R-chemo + ASCT versus R-chemo alone, were 67% versus 48% (P = 0.11) and 60% versus 30% (P = 0.02), respectively. Furthermore, in 'Composite/discordant TIL' R-chemo + ASCT showed no impact on OS (76% versus 67%; P = 0.66) or PFS (71% versus 62%; P = 0.54). Conversely, R-chemo + ASCT improved the outcome of 'sequential TIL' (OS 62% versus 36%; P = 0.07; PFS 53% versus 6%; P = 0.002), regardless of prior rituximab therapy. The beneficial effect of ASCT was significantly higher in patients who had not received rituximab at IL stage. CONCLUSIONS: ASCT improved the outcome in sequential, but not composite/discordant TIL. The beneficial impact of ASCT was greater in patients, who were rituximab-naïve at transformation.

[Primary cerebral non-Hodgkin's lymphomas and primary malignant brain tumors in a well-defined geographical area. Population-based data from the registry of non-Hodgkin's lymphoma in western Denmark, LYFO and the cancer registry, Kraeftens Bekaempelse]. / Primaere cerebrale non-Hodgkins lymfomer og primaere maligne hjernetumorer i et veldefineret geografisk område. Populationsbaserede data fra det vestdanske non-Hodgkins lymfom-register, LYFO, og Cancerregisteret, Kraeftens Bekaempelse.

In a Danish population-based non-Hodgkin's lymphoma (NHL) registry (LYFO) representing a population of 2.7 million all new cases of NHL were registered from 1st January 1983 to 31st May 1994. Incidence data of primary malignant tumours of the brain and central nervous system in western Denmark for the period 1971-1990 have been obtained from the Danish Cancer Registry. During the approximate 11-year period 3124 new cases of NHL were registered. Of these, 1152 (37%) were extranodal and 48 were non-AIDS related primary central nervous system lymphomas (PCNSL) accounting for 4.2% of extranodal NHL and 1.5% of all NHL, respectively. The average annual incidence rate of non-AIDS related PCNSL during the period was 1.56 cases per million population (age range: 15-85 yrs, median: 62 yrs, M/F ratio: 1). In a 23-year period there was no trend towards an increasing incidence of non-AIDS related PCNSL in a well-defined population. PCNSL accounted for 1.7% of all primary malignant brain tumours. Incidence of primary malignant brain tumours was stable, except for age ranges over 70 years. Histologically, 85% were high grade, centroblastic diffuse (60%) and immunoblastic lymphoma (13%) (Kiel classification). No T-cell lymphomas were detected. Treatment included surgical resection, whole brain irradiation (WBRT) and chemotherapy. Median survival for those receiving either WBRT or WBRT and chemotherapy was eight months and 20 months, respectively (p = 0.78). Overall survival was 53%, 38% and 26% at one, two and five years. Cox-regression analysis identified only one factor having independent impact on survival in performance score > or = 2 (PCNSL p < 0.001, RR = 5.8).

[Non-Hodgkin lymphoma in the elderly]. / Non-Hodgkin's lymfom hos aeldre.

Within a seven year period, 1597 newly diagnosed cases of non-Hodgkins lymphoma (NHL) were included in a Danish population-based NHL-register. Of these, 602 (38%) were aged 70 or older (age range 70-94, median: 76.8) and represented the population defined as "elderly" patients in the present study. Their average annual incidence rate was 35.7/10(5), as compared to 6.6/10(5) for patients aged < 70 (overall annual incidence: 9.5/105). Localised cases (stage I and II) and extranodal manifestations were more frequent among elderly patients. The most common sites of extranodal involvement were stomach (21% of all extranodal cases) and bone marrow (16%). Histologically, follicular centroblastic/centrocytic cases were found to be less frequent (p < 0.01) in elderly patients as compared to their younger counterparts (< 70 years), who on the other hand had a lower occurrence of diffuse centroblastic cases (p < 0.01). Overall seven year survival for the elderly patient population was 35% (median: 1.7 years), and for patients aged < 70 it was 57%. This difference persisted after correction for apparently NHL-unrelated deaths (52% vs. 66% respectively, p < 0.0001). The following poor prognostic factors for elderly patients were identified by multivariate analysis: hepatic involvement, presence of B-symptoms, high-grade histology and elevated s-LDH. The corresponding relative risk values were respectively 2.4, 2.2, 1.9 and 1.6.

[Immunosuppression with cyclosporin induces clinical remission and improved beta cell function in patients with newly diagnosed insulin-dependent diabetes. A national and international multicenter study]. / Immunosuppression med ciklosporin inducerer klinisk remission og forbedret beta-cellefunktion hos patienter med nykonstateret insulinkraevende diabetes. En national og international multicenterundersøgelse. The Canadian-European Randomized Control Trial Group.

A prospective, randomized, double-blind, placebo-controlled international multicenter trial including 188 newly diagnosed insulin-dependent diabetic (IDDM) patients was undertaken with the aim of investigating whether immunosuppression for one year with ciklosporin (Cs) could induce and maintain clinical remission and improvement of beta-cell function. The relative odds for non-insulin-requiring remission at one year were increased approximately five times in the Cs-treated group. After three months Cs-treated patients achieved more than a doubling of beta-cell function compared to baseline than did placebo-treated patients, and the Cs-treated group maintained this improvement in beta-cell function for 12 months, whereas the placebo-group lost beta-cell function during the same period. Short duration of disease (less than or equal to six weeks of symptoms, less than or equal to two weeks of insulin treatment) was associated positively with remission, as was an elevated proinsulin/C-peptide ratio, especially in patients with the tissue-type HLA-DR 3,4; 4,X and X,X. Cs-treatment inhibited the formation of antibodies against insulin and islet cell components, but islet cell antibody status at entry was not predictive of remission. Cs-treatment caused a reversible decrement of kidney function as measured with serum creatinine and the calculated creatinine clearance, but studies of renal physiology and kidney biopsies performed on a limited subset of patients indicated that Cs treatment in IDDM patients for one year induced a slight chronic nephropathy in some of these.(ABSTRACT TRUNCATED AT 250 WORDS)