Impact of time since diagnosis and mortality rate on cancer-associated venous thromboembolism: the Scandinavian Thrombosis and Cancer (STAC) cohort.

Essentials Competing risk by death may lead to overestimation of venous thromboembolism (VTE) risk in cancers. We assessed the risk of VTE in cancer with and without accounting for competing risk by death. The risk of VTE was influenced by the mortality rate and the time since cancer diagnosis. Competing risk by death should be taken into account when exploring VTE risk in cancer. SUMMARY: Background Venous thromboembolism (VTE) is a common complication in cancer, and studies have suggested that aggressive cancers create the highest risk of VTE. However, competing risk by death may result in overestimation of VTE risk in patients with cancers associated with high mortality. Therefore, we estimated the risk of VTE by cancer site, accounting for the differential mortality between cancers. Methods The Scandinavian Thrombosis and Cancer cohort included 144 952 participants followed from 1993-1997 to 2008-2012. Incidence rates, cause-specific hazard ratios (HRs) and subdistribution HRs (SHRs) were assessed for overall cancer and by cancer site according to time intervals since cancer diagnosis. Results During follow-up, 14 272 subjects developed cancer, and 567 had cancer-related VTE. In cause-specific analyses, the VTE risk was highest in the first 6 months after cancer diagnosis (HR 17.5, 95% confidence interval [CI] 15.1-20.3), and declined rapidly thereafter. However, when mortality was taken into account, the risk was similar in the periods 6 months before (SHR 4.8, 95% CI 3.6-6.4) and 6 months after (SHR 4.6, 95% CI 3.9-5.4) cancer diagnosis. The range of the 2-year cumulative VTE incidence rates was substantially narrowed for all cancer sites after competing risk by death was taken into account (from 1-10% to 1-4%). Conclusion VTE risk by cancer site was influenced by the mortality rate and the time since cancer diagnosis. Our findings suggest that the cancer itself is a major contributor to VTE risk, and that competing risk by death should be taken into account when VTE risk in cancer is explored.

The impact of initial cancer stage on the incidence of venous thromboembolism: the Scandinavian Thrombosis and Cancer (STAC) Cohort.

Essentials Impact of cancer stage on venous thromboembolism (VTE) risk is not well-known in all cancers. The Scandinavian Thrombosis and Cancer Cohort provides person-time data and validated VTEs. Impact of cancer stage on VTE incidence tended to vary with cancer type. Cancer stage may not per se be a risk factor for VTE in all cancer types. SUMMARY: Background Absolute measures of the impact of cancer stage on the incidence of venous thromboembolism (VTE) in patients with distinct cancer types have not been investigated in a large population-based cohort study. Objectives To investigate differences in the incidence rates of objectively confirmed VTE according to the development of cancer in a large population-based cohort study. Cancer type and stage at the time of diagnosis were taken into account. Patients and Methods The Scandinavian Thrombosis and Cancer Cohort includes data regarding cancer types, stages and objectively confirmed VTE diagnoses among 144 952 participants followed from 1993 to 2012. We studied stage-specific incidence rates of VTE, and calculated incidence rate differences (IRDs) for VTE according to stages in patients with 10 types of solid cancer. Results During the entire follow-up, 335 VTEs occurred, of which 293 occurred within 5 years. The IRD of VTE in patients with distant metastasis as compared with those with localized disease indicated large variation depending on cancer type. The highest IRD was observed for pancreatic cancer (IRD of 187.0 × 10-3 person-years [p-y]; 95% confidence interval [CI] - 6.7 to 380.8), and the lowest IRD was observed for prostate cancer (IRD of 3.7 × 10-3 p-y; 95% CI - 7 to 15.2). Regional spread as compared with localized disease also indicated large variation depending on cancer type; the highest IRD was observed for uterine cancer (IRD of 37.6 × 10-3 p-y; 95% CI - 23.7 to 99), and the IRDs for breast and prostate cancer were close to zero. Conclusion More advanced cancer at the time of diagnosis was associated with a higher risk of VTE, but the strength of the associations differed substantially between cancer types.

Benzylpenicillin plus an aminoglycoside versus meropenem in neutropenic lymphoma and leukaemia patients with a suspected bacterial infection: a randomized, controlled trial.

OBJECTIVES: In Norway, initial treatment of febrile neutropenia (FN) has traditionally been benzylpenicillin plus an aminoglycoside. Internationally, FN is often treated with a broad-spectrum ß-lactam antibiotic. We aimed to compare these two regimens in a prospective, randomized, trial in patients with lymphoma or leukaemia with an expected period of neutropenia ≥7 days, and a suspected bacterial infection. METHODS: Adult neutropenic patients with lymphoma or leukaemia, and a suspected bacterial infection, were randomized for treatment with benzylpenicillin plus an aminoglycoside or meropenem. The primary endpoint was clinical success, defined as no modification of antibiotics and clinical stability 72 h after randomization. RESULTS: Among 322 randomized patients, 297 proved evaluable for analyses. Fifty-nine per cent (95% CI 51%-66%), (87/148) of the patients given benzylpenicillin plus an aminoglycoside were clinically stable, and had no antibiotic modifications 72 h after randomization, compared with 82% (95% CI 75%-87%), (122/149) of the patients given meropenem (p <0.001). When the antibiotic therapy was stopped, 24% (95% CI 18%-32%), (36/148) of the patients given benzylpenicillin plus an aminoglycoside, compared with 52% (95% CI 44%-60%), (78/149) of the patients given meropenem, had no modifications of their regimens (p <0.001). In the benzylpenicillin plus an aminoglycoside arm, the all-cause fatality within 30 days of randomization was 3.4% (95% CI 1.2%-7.9%), (5/148) of the patients, compared with 0% (95% CI 0.0%-3.0%), (0/149) of the patients in the meropenem arm (p 0.03). CONCLUSION: Clinical success was more common in FN patients randomized to meropenem compared with the patients randomized to benzylpenicillin plus an aminoglycoside. The all-cause fatality was higher among the patients given benzylpenicillin plus an aminoglycoside.

Autologous stem cell transplantation versus novel drugs or conventional chemotherapy for patients with relapsed multiple myeloma after previous ASCT.

High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is the most common first-line treatment for patients with multiple myeloma (MM) under 65 years of age. A second ASCT at first relapse is frequently used but is challenged by the use of novel drugs. We retrospectively studied the outcome of second-line treatment in MM patients from the Nordic countries with relapse after first-line HDT and ASCT. Patients that underwent a second ASCT (n=111) were compared with patients re-treated with conventional cytotoxic drugs only (n=91) or with regimens including novel drugs (proteasome inhibitors and/or immunomodulatory drugs) (n=362) without a second ASCT. For patients receiving a second ASCT median overall survival was 4.0 years compared with 3.3 years (P<0.001) for the group treated with novel drugs and 2.5 years (P<0.001) for those receiving conventional cytotoxic drugs only. A second ASCT also resulted in a significantly longer second time to progression and a significantly longer time to next treatment. We conclude that, irrespective of the addition of novel drugs, MM patients in first relapse after ASCT still appear to benefit from a second ASCT. A second ASCT should be considered for all physically fit patients.

The relationship between body mass index, activated protein C resistance and risk of venous thrombosis.

BACKGROUND: High body mass index (BMI) is associated with an increased risk of venous thrombosis (VT). Clotting factor VIII levels are increased in obese subjects, possibly because of a chronic inflammatory state, which increases activated protein C (APC) resistance. The APC resistance in FV Leiden carriers could be aggravated and further worsened by high FVIII levels in blood group non-O carriers. We hypothesized that an association exists between BMI and APC resistance, and that this is amplified by the presence of FV Leiden and/or blood group non-O. METHODS: We used the Leiden Thrombophilia Study (LETS) to determine whether an association exists between BMI and APC resistance, and whether the combination of high BMI and APC resistance increases the risk of VT. In a pooled analysis of LETS and a Norwegian case-cohort study (TROL), we verified whether FV Leiden modified the risk of the occurrence of VT with increasing BMI, and whether this risk was further increased by blood group non-O. RESULTS: APC resistance increased linearly with increasing BMI, partly because of a concurrent rise in FVIII. A BMI in the median or upper tertile was associated with a 1.9-fold (95% confidence interval [CI] 1.0-2.5) and 2.2-fold (95% CI 1.4-3.4) increased risk as compared with the lowest tertile. Both relative risks decreased slightly after FVIII and APC resistance adjustments. The effect of BMI on VT risk was enhanced two-fold to 10-fold in FV Leiden or blood group non-O carriers. CONCLUSIONS: The increased risk of VT in individuals with high BMI is partly mediated by FVIII-related APC resistance. This risk is more pronounced when other causes of increased APC resistance are also present.

Increased levels of free thyroxine and risk of venous thrombosis in a large population-based prospective study.

BACKGROUND: Recent studies have shown that high levels of free thyroxine (FT4), even without leading to hyperthyroidism, are associated with a procoagulant state. OBJECTIVES: The aim of our study was to determine whether high levels of thyroid hormones are associated with an increased risk of venous thrombosis. PATIENTS/METHODS: From a prospective nested case-cohort design within the second Nord-Trøndelag Health Study (HUNT2) cohort (1995-1997; 66,140 subjects), all patients with venous thrombosis during follow-up (n=515) and 1476 randomly selected age-stratified and sex-stratified controls were included. Relative and absolute risks for venous thrombosis were calculated for different cut-off levels of thyroid hormones on the basis of percentiles in the controls and different times between blood sampling and thombosis. RESULTS: In subjects with an FT4 level above the 98th percentile (17.3 pmol L(-1)), the odds ratio (OR) was 2.5 (95% confidence interval [CI] 1.3-5.0) as compared with subjects with levels below this percentile. For venous thrombosis within 1 year from blood sampling, this relative risk was more pronounced, with an OR of 4.8 (95% CI 1.7-14.0). Within 0.5 years, the association was even stronger, with an OR of 9.9 (95% CI 2.9-34.0, adjusted for age, sex, and body mass index). For thyroid-stimulating hormone, the relationship was inverse and less pronounced. The absolute risk within 6 months in the population for FT4 levels above the 98th percentile was 6.1 per 1000 person-years (95% CI 1.7-15.7). CONCLUSIONS: Levels of FT4 at the upper end of the normal range are a strong risk factor for venous thrombosis. The risk increased with higher levels of thyroxine and shorter time between blood sampling and thrombosis. Further studies on the effect of clinical hyperthyroidism are warranted.

Incidence and mortality of venous thrombosis: a population-based study.

BACKGROUND: Estimates of the incidence of venous thrombosis (VT) vary, and data on mortality are limited. OBJECTIVES: We estimated the incidence and mortality of a first VT event in a general population. METHODS: From the residents of Nord-Trøndelag county in Norway aged 20 years and older (n = 94 194), we identified all cases with an objectively verified diagnosis of VT that occurred between 1995 and 2001. Patients and diagnosis characteristics were retrieved from medical records. RESULTS: Seven hundred and forty patients were identified with a first diagnosis of VT during 516,405 person-years of follow-up. The incidence rate for all first VT events was 1.43 per 1000 person-years [95% confidence interval (CI): 1.33-1.54], that for deep-vein thrombosis (DVT) was 0.93 per 1000 person-years (95% CI: 0.85-1.02), and that for pulmonary embolism (PE) was 0.50 per 1000 person-years (95% CI: 0.44-0.56). The incidence rates increased exponentially with age, and were slightly higher in women than in men. The 30-day case-fatality rate was higher in patients with PE than in those with DVT [9.7% vs. 4.6%, risk ratio 2.1 (95% CI: 1.2-3.7)]; it was also higher in patients with cancer than in patients without cancer [19.1% vs. 3.6%, risk ratio 3.8 (95% CI 1.6-9.2)]. The risk of dying was highest in the first months subsequent to the VT, after which it gradually approached the mortality rate in the general population. CONCLUSIONS: This study provides estimates of incidence and mortality of a first VT event in the general population.

Quality assessment of autografting by probability evaluation: model estimation by clinical end-points in newly diagnosed multiple myeloma patients.

BACKGROUND: Pre-transplant clinical evaluation of autografting is an important step in predicting post-transplant support, complications and safety. Today, unfavorable outcomes such as early death or graft failure are rare, making them unsuitable for quality assessment of supportive autografting. However, end-points constructed from frequently occurring clinical events may estimate clinically relevant prognostic models. METHODS: The present retrospective analysis was based on two consecutive clinical trials in the Nordic area including up to 640 newly diagnosed multiple myeloma patients. RESULTS: In the model, the efficacy (time on antibiotics and use of transfusions) was influenced by pre-transplant variables, including sex, nationality, serum creatinine, hemoglobin, disease stage at diagnosis, response following induction therapy, length of priming and average graft CD34+ cell number per day of harvest. The toxicity end-point (time to blood cell recovery) was influenced by nationality, marrow plasma cell percentage, serum creatinine, M-component isotype, response to induction therapy, length of priming and graft CD34+ cell number. The safety (early disease recurrence or death) was influenced by serum creatinine, hemoglobin, treatment response and CD34+ cell number. DISCUSSION: In conclusion, the model illustrates that intervention strategies in quality assessment of autografting may benefit from probability estimates of graded clinical end-points.

Treatment of Burkitt's/Burkitt-like lymphoma in adolescents and adults: a 20-year experience from the Norwegian Radium Hospital with the use of three successive regimens.

BACKGROUND: Burkitt's/Burkitt-like lymphoma (BL/BLL) are highly aggressive lymphomas mainly affecting children and young adults. We report the results in adolescent and adult patients with the use of three successive regimens. PATIENTS AND METHODS: Forty-nine patients aged 15-70 years admitted to the Norwegian Radium Hospital in the period 1982-2001 with a diagnosis of BL/BLL on histological review and who were given chemotherapy with curative intent are included in this analysis. Up to 1987 patients were given doxorubicin-based chemotherapy supplemented with intravenous and intrathecal methotrexate (MmCHOP). From 1987 to 1994, patients who obtained complete remission upon this regimen were consolidated with high-dose therapy with stem-cell support (MmCHOP + HDT). In 1995 we introduced as frontline therapy the German Berlin-Frankfurt-Munster (BFM) regimen. RESULTS: By intention to treat analyses, the progression-free survival rates for patients who received MmCHOP (n=13), MmCHOP + HDT (n=17) or BFM therapy (n=19) are 30.8%, 70.6% and 73.7%, respectively. In the groups of patients who received either the BFM regimen or MmCHOP + HDT, all patients who obtained complete remission upon induction therapy are continuously disease free. There was no treatment-related death. CONCLUSIONS: BL/BLL in adolescents and adults can successfully be treated with 5-day blocks of intensified chemotherapy such as the BFM regimen or CHOP/methotrexate-based chemotherapy consolidated with high-dose therapy. Using the BFM regimen, continuous remissions are obtained without additional myeloablative chemotherapy.

[High dose therapy with autologous stem cell support--finally a progress in myelomatosis]. / Høydosebehandling med autolog stamcellestøtte--endelig et fremskritt ved myelomatose.

BACKGROUND: Since the introduction of the simple cyclic oral treatment with melphalan and prednisone in the late 1960s, there has been no substantial improvement in the therapy of multiple myeloma. In 1994, the Nordic Myeloma Study Group initiated a population-based, prospective study to evaluate the impact on survival of high dose chemotherapy in newly diagnosed, symptomatic patients under 60 years of age, compared to a conventionally treated control group. MATERIAL AND METHODS: 274 patients were treated according to a specified high dose protocol and compared to 274 patients from previous population-based trials fulfilling the same eligibility criteria. RESULTS: Median survival was 44 months in the control group and 62 months in the intensive treatment group (risk ratio 1.65; 95% CI = 1.28-2.14, P = 0.0001). A study of health-related quality of life (HRQoL) which was integrated in the trial showed a moderately reduced HRQoL associated with the intensive treatment phase, but no statistically significant difference beyond the first year of follow-up. In a cost-utility analysis of the trial, the cost per (quality-adjusted life years) was estimated at USD 26,000. INTERPRETATION: The incremental cost of the treatment is within what is usually thought to be acceptable limits. Further improvement of the results and reduction of stay in hospital would give an even more favourable cost-utility ratio.

Renal histopathology and clinical course in 94 patients with Wegener's granulomatosis.

BACKGROUND: The main purpose of this study was to examine histopathological changes seen in renal biopsies from patients with Wegener's granulomatosis (WG) with varying degrees of renal involvement and to study possible correlations between the morphological variables and the severity of the disease. METHODS: Ninety-four patients with WG and active renal disease were included in this retrospective study. All patients had a percutaneous renal biopsy taken on their first admission to the hospital and 14 patients had a second biopsy. The patients were followed for a median of 42.5 months (range 0.5-184). RESULTS: Segmental necrotizing glomerulonephritis and extracapillary proliferation were present in 85.1 and 91.5% respectively. Of seven patients (7.4%) with normal serum creatinine and urinary protein excretion <0.5 g/day, all had crescents and six had segmental glomerular necrosis. Serum creatinine at biopsy correlated significantly with the percentage of glomeruli with crescents (rho=0.52, P=0.0004), with necrosis (rho=0.36, P=0.002) and with the percentage of normal glomeruli (rho=-0.55, P=0.0003). On a multivariate analysis, only the percentage of normal glomeruli was significantly associated with renal function and development of end-stage renal disease. In 14 second biopsies after a mean of 41.2 (+/-26) months, chronicity scores had increased significantly in 13 biopsies in spite of full immunosuppressive treatment. CONCLUSION: Although renal biopsy is of value in defining renal involvement in WG, it is of limited help in the early stage of the disease in predicting renal outcome for the individual patient. A follow-up biopsy can be useful in revealing the degree of activity and chronicity and hence be of importance for the choice of further therapy.

Wegener's granulomatosis: inflammatory cells and markers of repair and fibrosis in renal biopsies--a clinicopathological study.

OBJECTIVE: This study aimed to quantitate inflammatory cells in renal biopsies from patients with Wegener's granulomatosis (WG) and to identify cells participating in early fibrogenesis. The goal was to determine whether these cells correlated with the severity of renal disease and whether their presence had a bearing on renal prognosis. MATERIAL AND METHODS: Sixty-one patients with WG who had a renal biopsy taken at the time of diagnosis were included in the study. Immunostaining with monoclonal antibodies towards macrophages (CD68), T- and B-lymphocytes, alpha-smooth muscle actin (alpha-SMA) and vimentin was done. RESULTS: The dominating intraglomerular leucocytes were macrophages (29.9 +/- 15 cells/glomerular cross-section) and to a lesser extent T-cells (2.57 +/- 1.8 cells/glomerular cross-section). No B-lymphocytes were detected in the glomeruli. More than two-thirds of the T-cells were CD8+ (cytotoxic) cells. Macrophages and T-lymphocytes were distributed equally in the renal interstitium and were numerous around crescentic glomeruli. Glomerular and interstitial macrophages and interstitial T-cells correlated significantly with serum (S-) creatinine at the time of biopsy but not after 1 year. S-creatinine at the time of biopsy and after 1 year differed significantly among the three levels of interstitial alpha-SMA staining. S-creatinine at biopsy was highest when tubular vimentin staining was strongest, and tubular vimentin staining was strongest in patients with acute tubular damage. CONCLUSIONS: Evidence was found for a cellular type IV immune response in WG, with CD8+ T-lymphocytes and macrophages dominating the cellular infiltrate. The detection of interstitial alpha-SMA, probably staining myofibroblasts implicated in renal fibrogenesis, indicated a low glomerular filtration rate 1 year after renal biopsy.

Wegener's granulomatosis: clinical course in 108 patients with renal involvement.

BACKGROUND: The aim of this study was to evaluate the clinical course of patients with Wegener's granulomatosis and renal involvement, with special reference to relapse rate, renal and patient survival and morbidity from serious infections. METHODS: A retrospective analysis was carried out of 108 patients presenting with Wegener's granulomatosis and active renal disease in eight hospitals in Norway between 1988 and 1998. Multivariate analysis was used to investigate whether selected variables predicted relapse, renal and patient survival and serious infections. RESULTS: Median follow-up was 41.5 months. Twenty-two patients (20.4%) were admitted with a need for dialysis. Complete remission was obtained in 81.5% after a median of 4 months, and 54.7% relapsed after a median of 22. 5 months. Two- and five-year renal survival was 86 and 75%, respectively, and 22.8% developed end-stage renal disease (ESRD). Two- and five-year patient survival was 88 and 74%, respectively, and the cumulative mortality was 3.8 times higher than expected. The relative risk of relapse increased with the use of intravenous pulse cyclophosphamide compared with daily oral cyclophosphamide. Initial renal function predicted renal survival, and low serum albumin and high age at treatment start increased the mortality risk. Thirty one per cent of the patients were hospitalized for serious infections during follow-up. Old age increased the risk of having an infection. CONCLUSIONS: The current treatment of Wegener's granulomatosis does not prevent relapse, development of ESRD and serious treatment-induced infections in a considerable fraction of the patients. Alternative strategies for the management of this disease will be an important objective for further studies.

Renal involvement in primary Sjögren's syndrome.

Renal involvement was evaluated in 62 patients with primary Sjögren's syndrome, classified according to criteria proposed by The European Classification Criteria Group. Urine concentration capacity was tested using intranasal 1-desamino-8-D-arginine-vasopressin. For patients with urine pH>5.5 without metabolic acidosis (n=28), an acidification test with ammonium chloride was performed. Urinary citrate, albumin, NAG, ALP and beta2-microglobulin were measured and creatinine clearance was calculated. Maximum urine concentration capacity and creatinine clearance were reduced in 13 (21%). Albumin excretion was >30 microg/min in only one patient (1.6%). Seven patients (11.3%) had complete or incomplete distal renal tubular acidosis (dRTA), four had reduced creatinine clearance and five had reduced maximum urine concentration capacity. The ratio of citrate/creatinine in spot urine was below the 2.5 percentile in all patients with complete or incomplete dRTA. The prevalence of dRTA was lower than in previous studies. There were also few patients with signs of glomerular disease (1.6%). The use of citrate:creatinine ratio in spot urine can be a helpful method in identifying patients with complete or incomplete dRTA.

Acute myeloid leukemia with inv(8)(p11q13).

A patient with acute monoblastic leukemia (AML M5a) and the pericentric inversion inv(8)(p11q13) as well as additional chromosome abnormalities in her bone marrow cells is described. This is the fourth known case of inv(8)(p11q13)-positive acute leukemia, and the second such case in which gain of 1q material occurred during clonal evolution. All patients with acute leukemia and inv(8)(p11q13) have been females, most have been young, and there has been a tendency for the disease to run an aggressive course. Both hematologically and cytogenetically, therefore, inv(8)(p11q13)-positive leukemia may be viewed as a variant of AML with t(8;16)(p11;p13). This similarity is also apparent at the molecular genetic level, in-as-much as the MOZ gene in 8p11 is rearranged in both the translocation and the inversion; in t(8;16)-positive leukemia, a MOZ-CBP chimeric gene is generated, whereas inv(8) has been shown to generate a MOZ-TIF2 fusion gene. Southern blot analysis of the present case after MOZ0.8 hybridization of Bam HI digested DNA gave an 11 kb aberrant band in addition to the germline band, corresponding to a breakpoint immediately upstream of the 4 kb long MOZ exon that begins at position 3746. Also previously investigated inv(8)-positive leukemias have shown breaks in this intron indicating that it contains sequence motifs predisposing to illegitimate recombination.

[Chronic lymphatic leukemia. A population-based study of symptoms, findings, complications and choice of treatment]. / Kronisk lymfatisk leukemi. En populasjonsbasert undersøkelse av symptomer, funn, komplikasjoner og behandlingsvalg.

224 patients with a recent diagnosis of chronic lymphocytic leukemia, confirmed by immune phenotype, were studied with a mean follow-up of 16 months. The median age was 72 years and the ratio of men to women was 1.51. An incidental diagnosis because of leukocytosis was made in 75% of the patients; in only 22% was the diagnosis related to symptoms. 80% were in stage A, 7.5% in stage B, and 12.5% in stage C. A relation was found between advanced stage and the number of lymphocytes in the blood, the percentage of lymphocytes in the bone marrow, WHO performance status, bacterial infection and disease-related mortality. Thus, six patients in stage C (21%) died because of infection (septicaemia or pneumonia), as opposed to only one out of 196 patients in stages A and B. The incidence of bacterial infection was 64% in stage C, as compared to 8.3% in stage A. Treatment with chlorambucil, started in 59 patients, was in accordance with the guidelines of the national programme for 52 of them. In contrast, a strict indication for prednisone (autoimmune cytopenia) was found in only 42% of 42 patients given this treatment.

[Chronic lymphatic leukemia. Immunophenotyping as an aid to correct diagnosis]. / Kronisk lymfatisk leukemi. Immunfenotyping som hjelpemiddel for riktig diagnose.

The purpose of the study was to examine the validity of the primary diagnosis in chronic lymphocytic leukemia based on clinical and morphological criteria, and to examine the role of immune phenotyping for correct diagnosis in an unselected population-based group of patients. Over a 2-year period leukemic cells from 222 of 235 patients in Norway with a recent clinical diagnosis of chronic lymphocytic leukemia (CLL) were immune phenotyped in order to find cases erroneously diagnosed as CLL. Median age was 72.5 years, and the ratio of men to women was 1.47. At the time of diagnosis, 77% of the patients were in Binet stage A and 23% in stage B or C. Immune phenotyping, in some patients followed by lymph node or bone marrow biopsy, showed a different diagnosis in 11 (5%) of 222 patients: prolymphocytic leukemia, four patients (three B-cell and one T-cell); morbus Waldenstrøm, one patient; T-cell CLL, one patient; hairy cell leukemia, one patient; mycosis fungoides, one patient; mantle cell lymphoma, one patient; monocytoid B-cell lymphoma, one patient and immunoblastic lymphoma one patient. In eight of these 11 patients, the clinical features or morphology, or both, were atypical for CLL, but this was not recognized at the time of diagnosis. Thus, immune phenotyping is valuable for correct diagnosis in a small subgroup of patients with chronic B- or T-cell leukemia, and it is essential in patients with modest lymphocytosis (lymphocytes < 10. 10(9)/1).