N-terminal pro-C-type natriuretic peptide in serum associated with bone destruction in patients with multiple myeloma.

AIM: To examine whether N-terminal proCNP concentrations in serum is associated with bone destruction in patients with multiple myeloma. MATERIALS & METHODS: N-terminal proCNP and biochemical bone markers were measured in 153 patients. Radiographic bone disease and skeletal-related events were evaluated at specific time-points. RESULTS: N-terminal proCNP concentrations increased with age. High N-terminal proCNP concentrations were associated with high-risk disease and renal impairment. Renal function explained 22% of the variation. N-terminal proCNP concentrations correlated with serum bone ALP and serum PINP, but lacked association with bone resorption markers, radiographic bone disease and skeletal-related events. CONCLUSION: Serum N-terminal proCNP are associated with bone formation activity in patients with multiple myeloma, but should be interpreted with caution in patients with renal impairment.

Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial.

The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370 patients were centrally randomly assigned 3 months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation. The hypothesis was that consolidation therapy would prolong progression-free survival (PFS). The PFS after randomization was 27 months for the bortezomib group compared with 20 months for the control group (P = .05). Fifty-one of 90 patients in the treatment group compared with 32 of 90 controls improved their response after randomization (P = .007). No difference in overall survival was seen. Fatigue was reported more commonly by the bortezomib-treated patients in self-reported quality-of-life (QOL) questionnaires, whereas no other major differences in QOL were recorded between the groups. Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response (VGPR) but not for patients in the ≥ VGPR category at randomization. Consolidation with bortezomib after ASCT in bortezomib-naive patients improves PFS without interfering with QOL. This trial was registered at www.clinicaltrials.gov as #NCT00417911.

Low prevalence of hereditary hemochromatosis in multiethnic populations in Northern Norway.

OBJECTIVE: Hereditary hemochromatosis has an autosomal recessive inheritance. The C282Y homozygosity is the most common genetic mutation in persons of Northern European descent. A screen of two multiethnic populations in Northern Norway was performed to investigate whether the prevalence of hereditary hemochromatosis was consistent with previous results in Northern Europe. MATERIAL AND METHODS: Participants in two population-based studies in Northern Norway were analyzed for serum ferritin (s-ferritin) and transferrin saturation. Participants with s-ferritin or transferrin saturation above the reference limits in two separate blood samples were tested for three different HFE mutations, namely C282Y, H63D and S65. RESULTS: The estimated prevalence of the C282Y/C282Y mutation in the two municipalities studied was lower than in comparable studies in Norway. The prevalence was the lowest in the Sør-Varanger population (men 0.19% and women 0.22%), which also had the highest proportion of individuals with Sami and Kven affiliation. In Tromsø, the prevalence was consistent with previous results in Norway. CONCLUSIONS: The prevalence of hereditary hemochromatosis is lower in multiethnic populations in Northern Norway than in previous studies from other parts of Norway.

Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial.

BACKGROUND: Compared with placebo, prophylactic treatment with bisphosphonates reduces risk of skeletal events in patients with multiple myeloma. However, because of toxicity associated with long-term bisphosphonate treatment, establishing the lowest effective dose is important. This study compared the effect of two doses of pamidronate on health-related quality of life and skeletal morbidity in patients with newly diagnosed multiple myeloma. METHODS: This double-blind, randomised, phase 3 trial was undertaken at 37 clinics in Denmark, Norway, and Sweden. Patients with multiple myeloma who were starting antimyeloma treatment were randomly assigned in a 1:1 ratio to receive one of two doses of pamidronate (30 mg or 90 mg) given by intravenous infusion once a month for at least 3 years. Randomisation was done by use of a central, computerised minimisation system. Primary outcome was physical function after 12 months estimated by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire (scale 0-100). All patients who returned questionnaires at 12 months and were still on study treatment were included in the analysis of the primary endpoint. This study is registered with ClinicalTrials.gov, number NCT00376883. FINDINGS: From January, 2001, until August, 2005, 504 patients were randomly assigned to pamidronate 30 mg or 90 mg (252 in each group). 157 patients in the 90 mg group and 156 in the 30 mg group were included in the primary analysis. Mean physical function at 12 months was 66 points (95% CI 62·9-70·0) in the 90 mg group and 68 points (64·6-71·4) in the 30 mg group (95% CI of difference -6·6 to 3·3; p=0·52). Median time to first skeletal-related event in patients who had such an event was 9·2 months (8·1-10·7) in the 90 mg group and 10·2 months (7·3-14·0) in the 30 mg group (p=0·63). In a retrospective analysis, eight patients in the pamidronate 90 mg group developed osteonecrosis of the jaw compared with two patients in the 30 mg group. INTERPRETATION: Monthly infusion of pamidronate 30 mg should be the recommended dose for prevention of bone disease in patients with multiple myeloma. FUNDING: Nordic Cancer Union and Novartis Healthcare.

Changes in body mass index and smoking habits have a different impact on hemoglobin concentration in men and women: a longitudinal follow-up of the Tromsø Study, 1994-2002.

BACKGROUND: Body mass index (BMI) and smoking have been positively associated with hemoglobin concentration, and both are risk factors for cardiovascular disease. OBJECTIVE: The aim of this study was to assess whether there were sex differences in how changes in BMI and smoking habits influenced hemoglobin concentration. METHODS: In 1994-95 and 2001-02, a longitudinal, population-based study was conducted in the municipality of Tromsø, in northern Norway. Inhabitants aged > or =25 years were invited to participate. Participants replied to a questionnaire regarding health, physical activity, coffee and alcohol consumption, and smoking habits. Blood samples were drawn to analyze hemoglobin concentration. All analyses were performed separately for each sex. Differences between 1994-95 and 2001-02 were examined with t or chi(2) (McNemar) tests for paired data. Cross-sectional comparisons were made using 2-sample t tests. Different models of univariate and multiple linear regression analyses were used to investigate the impact of the various variables on hemoglobin change. RESULTS: Data from a total of 2105 men and 2945 women were examined. At baseline, mean age was 58.9 years for men (range, 25-78 years) and 57.8 years for women (range, 25-82 years); mean BMI was 26.1 kg/m(2) for men and 25.8 kg/m(2) for women. In men, hemoglobin decreased with age, on average from 147.5 to 145.1 g/L. In women, hemoglobin decreased from 135.6 to 134.7 g/L, but increased with increasing age up to 54 years, and thereafter decreased gradually. Mean BMI increased 0.8 kg/m(2) in men and 1.2 kg/m(2) in women. In total, 394 of 2057 men (19%) and 499 of 2889 women (17%) stopped smoking or smoked fewer cigarettes per day. In a univariate regression model, an increase of 1 kg/m(2) in BMI was associated with an increase in hemoglobin of 1.1 g/L (95% CI, 0.84 to 1.27) in men and 0.4 g/L (95% CI, 0.30 to 0.56) in women. In another univariate model, smoking cessation was associated with a decrease in hemoglobin of 1.9 g/L (95% CI, -3.32 to -0.56) in men and 1.7 g/L (95% CI, -2.93 to -0.56) in women. In men who smoked less and had a BMI increase of >2.5 kg/m(2), hemoglobin decreased 0.3 g/L. In contrast, hemoglobin decreased 3.4 g/L in men who smoked less and lost weight (P for trend, < 0.001 by changing BMI). Women who smoked less had a decrease in hemoglobin independent of BMI changes. CONCLUSIONS: The positive association between an increase in BMI and hemoglobin was stronger in men than in women. The effect of smoking reduction on hemoglobin was attenuated with increasing BMI in men, but not in women.

Identification of translocation products but not K-RAS mutations in memory B cells from patients with multiple myeloma.

BACKGROUND: Several laboratories have shown that cells with a memory B-cell phenotype can have the same clonotype as multiple myeloma tumor cells. DESIGN AND METHODS: The aim of this study was to determine whether some memory B cells have the same genetic alterations as their corresponding multiple myeloma malignant plasma cells. The methodology included sorting multiple myeloma or memory B cells into RNA stabilizing medium for generation of subset-specific polymerase chain reaction complementary DNA libraries from one or 100 cells. RESULTS: Cells with the phenotype of tumor plasma cells (CD38(++)CD19(-)CD45(-/+)CD56(-/+/++)) or memory B cells (CD38(-)/CD19(+)/CD27(+)) were isolated by flow activated cell sorting. In samples from all four patients with multiple myeloma and from two of the three with monoclonal gammopathy of undetermined significance, we identified memory B cells expressing multiple myeloma-specific oncogenes (FGFR3; IGH-MMSET; CCND1 high) dysregulated by an IGH translocation in the respective tumor plasma cells. By contrast, in seven patients with multiple myeloma, each of whom had tumor plasma cells with a K-RAS61 mutation, a total of 32,400 memory B cells were analyzed using a sensitive allele-specific, competitive blocker polymerase chain reaction assay, but no K-RAS mutations were identified. CONCLUSIONS: The increased expression of a specific "early" oncogene of multiple myeloma (monoclonal gammopathy of undetermined significance) in some memory B cells suggests that dysregulation of the oncogene occurs in a precursor B-cell that can generate memory B cells and transformed plasma cells. However, if memory B cells lack "late" oncogene (K-RAS) mutations but express the "early" oncogene, they cannot be involved in maintaining the multiple myeloma tumor, but presumably represent a clonotypic remnant that is only partially transformed.

Multiparametric flow cytometry profiling of neoplastic plasma cells in multiple myeloma.

BACKGROUND AND AIM: The clinical impact of multiparametric flow cytometry (MFC) in multiple myeloma (MM) is still unclear and under evaluation. Further progress relies on multiparametric profiling of the neoplastic plasma cell (PC) compartment to provide an accurate image of the stage of differentiation. The primary aim of this study was to perform global analysis of CD expression on the PC compartment and subsequently to evaluate the prognostic impact. Secondary aims were to study the diagnostic and predictive impact. DESIGN AND METHODS: The design included a retrospective analysis of MFC data generated from diagnostic bone marrow (BM) samples of 109 Nordic patients included in clinical trials within NMSG. Whole marrow were analyzed by MFC for identification of end-stage CD45(-) /CD38(++) neoplastic PC and registered the relative numbers of events and mean fluorescence intensity (MFI) staining for CD19, CD20, CD27, CD28, CD38, CD44, CD45, CD56, and isotypes for cluster analysis. RESULTS: The median MFC-PC number was 15%, and the median light microscopy (LM)-PC number was 35%. However, the numbers were significant correlated and the prognostic value with an increased relative risk (95% CI) of 3.1 (1.7-5.5) and 2.9 (1.4-6.2), P < 0.0003 and P < 0.004 of MFC-PC and LM-PC counts, respectively. Unsupervised clustering based on global MFI assessment on PC revealed two clusters based on CD expression profiling. Cluster I with high intensity for CD56, CD38, CD45, right-angle light-scatter signal (SSC), forward-angle light-scatter signal (FSC), and low for CD28, CD19, and a Cluster II, with low intensity of CD56, CD38, CD45, SSC, FSC, and high for CD28, CD19 with a median survival of 39 months and 19 months, respectively (P = 0.02). CONCLUSIONS: The MFC analysis of MM BM samples produces diagnostic, prognostic, and predictive information useful in clinical practice, which will be prospectively validated within the European Myeloma Network (EMN). © 2010 International Clinical Cytometry Society.

Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma.

In this double-blind, placebo-controlled study, 363 patients with untreated multiple myeloma were randomized to receive either melphalan-prednisone and thalidomide (MPT) or melphalan-prednisone and placebo (MP). The dose of melphalan was 0.25 mg/kg and prednisone was 100 mg given daily for 4 days every 6 weeks until plateau phase. The dose of thalidomide/placebo was escalated to 400 mg daily until plateau phase and thereafter reduced to 200 mg daily until progression. A total of 357 patients were analyzed. Partial response was 34% and 33%, and very good partial response or better was 23% and 7% in the MPT and MP arms, respectively (P < .001). There was no significant difference in progression-free or overall survival, with median survival being 29 months in the MPT arm and 32 months in the MP arm. Most quality of life outcomes improved equally in both arms, apart from constipation, which was markedly increased in the MPT arm. Constipation, neuropathy, nonneuropathy neurologic toxicity, and skin reactions were significantly more frequent in the MPT arm. The number of thromboembolic events was equal in the 2 treatment arms. In conclusion, MPT had a significant antimyeloma effect, but this did not translate into improved survival. This trial was registered at www.clinicaltrials.gov as #NCT00218855.

Regulation of the CD56 promoter and its association with proliferation, anti-apoptosis and clinical factors in multiple myeloma.

Multiple myeloma (MM) is an incurable B-cell malignancy characterised by uncontrolled growth and accumulation of malignant plasma cells in the bone marrow. Aberrant expression of CD56 in patients with MM is thought to contribute to a worsened disease course and metastasis. We therefore investigated the regulation of the CD56 promoter in relation to typical clinical factors. We used qPCR and FACS to measure the expression levels of CD56, and potential regulatory factors in patients with MM and related these with MM progression/prognosis. The transcription factors BTBD3, Pax5, RUNX1 and MMSET were positively associated with CD56 expression, as was CYCLIN D1, which is involved in disease progression, anti-apoptosis and proliferation. RUNX1 was negatively associated with the survival of stem-cell transplanted patients. Our findings propose four potential activators of the CD56 promoter and for CD56 to be involved in proliferation and anti-apoptosis, leading to disease progression in MM.

Myeloma cell expression of 10 candidate genes for osteolytic bone disease. Only overexpression of DKK1 correlates with clinical bone involvement at diagnosis.

Osteolytic bone disease (OBD) in multiple myeloma (MM) is caused by interactions between MM cells and the bone marrow microenvironment and is characterized by increased osteoclastic bone resorption and decreased osteoblastic bone formation. Recently, the role of osteoblast inhibition has come into focus, especially the possible role of overexpression of DKK1, an inhibitor of the Wnt signalling pathway. Further, CKS2, PSME2 and DHFR have also been reported as candidate genes for OBD. We studied the gene expression by quantitative reverse transcription polymerase chain reaction of TNFSF11 (RANKL), TNFSF11A (RANK), TNFRSF11B (OPG), CCL3 (MIP1A), CCL4 (MIP1B), PTHR1 (PTHrp), DKK1, CKS2, PSME2 and DHFR in purified, immunophenotypic FACS-sorted plasma cells from 171 newly diagnosed MM patients, 20 patients with monoclonal gammopathy of undetermined significance and 12 controls. The gene expressions of the analysed genes were correlated with radiographically assessed OBD. Only overexpression of DKK1 was correlated to the degree of OBD. Myeloma cells did not express TNFSF11A, TNFSF11, or TNFRSF11B, and very rarely expressed CCL3 and PTHR11. CCL4, CKS2, PSME2 and DHFR were variably expressed, but the expression of these genes showed no correlation with OBD. In contrast, loss of PSME2 expression in MM plasma cells was significantly correlated with OBD.

Dysregulation of CD47 and the ligands thrombospondin 1 and 2 in multiple myeloma.

CD47 and thrombospondin 1 and 2 (TSP1 and TSP2) expression were analysed by real-time reverse transcription polymerase chain reaction in fluorescence-activated cell sorted plasma cells (PCs) from patients at consecutive stages of multiple myeloma (MM) development. 80% of MM patients, but only 39% of patients with monoclonal gammopathy of undetermined significance (MGUS) expressed CD47; median expression level increased 10-fold with progression from MGUS to MM. Elevated TSP1/TSP2 levels occurred in bone marrow cultures from MM patients compared with healthy donors. CD47 and TSP1/TSP2 may have a potential role in the pathophysiology of MM, probably in the interaction between MM PCs and the microenvironment.

[A 40-year-old woman with anemia]. / En 40 år gammel kvinne med anemi.

BACKGROUND: Normally the body is unable to regulate its own iron content effectively by excretion. Urinary excretion of iron is about 10% of total daily loss. CASE PRESENTATION: A 40-year-old woman was admitted to hospital because of anaemia that turned out to be caused by iron deficiency. In spite of extensive investigations no cause of her iron deficiency was identified. The urine was then tested for iron and showed excessive urinary loss as the cause of her anaemia. To our knowledge, extensive urinary iron loss as the cause of iron deficiency has not been reported before.

Intensive therapy for multiple myeloma in patients younger than 60 years. Long-term results focusing on the effect of the degree of response on survival and relapse pattern after transplantation.

BACKGROUND AND OBJECTIVES: From 1994 to 1997 we conducted a population-based, prospective study on intensive therapy in newly diagnosed symptomatic myeloma patients younger than 60 years, comparing their survival to that of a conventionally treated historic population. Long-term results are presented, including the impact of the degree of response on survival and relapse pattern after transplantation. DESIGN AND METHODS: The prospective population was formed of 397 patients and the historic population of 313 patients. Both populations were calculated to comprise more than 75% of the expected number of new cases. RESULTS: After a median follow-up of 7 years survival was longer in the prospective population than in the historic one (median 60 versus 39 months; p=0.0002). When comparing only patients eligible for intensive therapy the median survival was 63 versus 44 months (p<0.0001). Attaining a complete response was associated with prolonged event-free survival but not overall survival. The pattern of relapse after transplantation was heterogeneous but could be divided into four major groups; insidious, classical, plasmacytoma form and transformed disease. The median survival after relapse was 29 months. The relapse pattern and time to relapse predicted outcome. Patients relapsing with an insidious or classical form of disease with skeletal events only, or after a long lasting first response were likely to respond well to conventional salvage therapy. In contrast, relapse with multiple symptoms, transformed disease or a short duration of first response implied bad prognosis. INTERPRETATION AND CONCLUSIONS: The relapse pattern after autologous transplantation is heterogeneous and response to salvage therapy is variable. The degree of response and event-free survival after transplantation are not reliable surrogate markers for survival.

Changes in haemoglobin levels according to changes in body mass index and smoking habits, a 20-year follow-up of a male cohort: the Tromsø Study 1974-1995.

Haemoglobin level declines with increasing age in cross sectional studies. Little is known about the longitudinal changes of haemoglobin. Because both high or low haemoglobin levels increase mortality and morbidity we examined how changes in lifestyle factors like body mass index (BMI) and smoking habits influence cohort changes in haemoglobin level. In all, 4159 men aged 20-49 years at baseline were examined in 1974 and 1994-1995 in a longitudinal, population-based study from the municipality of Tromsø, Northern Norway. Mean haemoglobin was 148 g/l. There was no difference in mean haemoglobin after 20 years in any strata of age. Mean BMI increased 2.1 kg/m(2). The prevalence of smokers decreased 20.1 percentage points. In a multiple regression analysis increase in BMI was associated with increased haemoglobin change. Smoking cessation lowered mean haemoglobin 1.6 g/l compared to never smokers. Haemoglobin increased 0.8 g/l in smoking quitters whose BMI increased >2.5 kg/m(2) compared to a decrease of 6.7 g/l in weight reducers. There was a positive dose-response relationship between changes in cigarettes smoked per day and change in haemoglobin among consistent smokers. In conclusion, in contrast to cross sectional studies, mean haemoglobin did not change during 20 years ageing of relatively young men. This could be explained by higher BMI and less smoking. The increase in BMI affected haemoglobin change to such an extent that the reduction in haemoglobin due to smoking cessation was counteracted. Prospective studies are needed to address the health implications.

Antithymocyte globulin and cyclosporine A as combination therapy for low-risk non-sideroblastic myelodysplastic syndromes.

The present study evaluated the combination of antithymocyte globulin (ATG) and cyclosporine A (CsA) in patients with low-risk myelodysplastic syndromes. Twenty patients (17 with refractory anemia and 3 with refractory anemia with excess blasts) received treatment with rabbit-ATG plus CsA. The overall response rate was 30% (6/20); three of the six responders had a complete response. The responses lasted 2-58 months, with two patients still being in complete remission at 42 and 58 months. Short-lasting cytogenetic remissions were achieved in two patients. ATG was poorly tolerated in patients over 70 years of age. Four out of 20 patients progressed to acute myeloid leukemia within a year. We conclude that immunosuppressive treatment may be a therapeutic option for selected patients with myelodysplastic syndrome.

Impact of age on survival after intensive therapy for multiple myeloma: a population-based study by the Nordic Myeloma Study Group.

The value of intensive therapy, including autologous stem cell transplantation, in newly diagnosed myeloma patients >60 years is not clear. We evaluated the impact of age (<60 years vs. 60-64 years) on survival in a prospective, population-based setting and compared survival with conventionally treated historic controls. The prospective population comprised 452 patients registered between 1998 and 2000. Of these, 414 received intensive therapy. The historic population, derived from our most recent population-based study on conventional therapy, comprised 281 patients. Of these, 243 fulfilled our eligibility criteria for intensive therapy. For patients undergoing intensive therapy it was found that two factors, beta-2-microglobulin and age <60 years vs. 60-64 years, had independent prognostic impact on survival. However, compared with the historic controls a survival advantage was found both for patients <60 (median 66 months vs. 43 months, P < 0.001) and 60-64 years (median 50 months vs. 27 months; P = 0.001). We conclude that in a population-based setting higher age adversely influences outcome after intensive therapy. Our results indicate that intensive therapy prolongs survival also at age 60-64 years but with less superiority than in younger patients.

Serum levels of iron in Sør-Varanger, Northern Norway--an iron mining municipality.

OBJECTIVES: The purpose of this study was to investigate iron status in a population with a high proportion of miners in the northernmost part of Norway. STUDY DESIGN: Cross-sectional, population-based study performed in order to investigate possible health effects of pollution in the population living on both sides of the Norwegian-Russian border. METHODS: All individuals living in the community of Sør-Varanger were invited for screening in 1994. In 2000, blood samples from 2949 participants (response rate 66.8 %), age range 30-69 years, were defrosted. S-ferritin and transferrin saturation were analysed in samples from 1548 women and 1401 men. About 30 % (n = 893) were employed in the iron mining industry, 476 of whom were miners and 417 had other tasks in the company. Type and duration of employment and time since last day of work at the company were used as indicators of exposure. RESULTS: Both s-ferritin levels and transferrin saturation were higher in men than in women. S-ferritin increased with increasing age in women, while the opposite was true for men. Iron deficiency occurred with higher frequencies in women (16 %) than in men (4 %). Iron overload was uncommon in both sexes. Adjustment for smoking and self-reported pulmonary diseases did not show any effect on iron levels. Miners had non-significant higher mean s-ferritin and transferrin saturation than non-miners. Neither duration, nor time since employment in the mine, had any impact on iron status. CONCLUSIONS: Our analyses did not show any associations between being a miner in the iron mining industry and serum iron levels compared to the general population.

Haemoglobin and anaemia in a gender perspective: the Tromsø Study.

OBJECTIVES: To examine the gender-specific distribution of haemoglobin (Hb) and the World Health Organization (WHO) criteria for anaemia compared with the 2.5 percentile for Hb. METHODS: A population-based study from Tromsø, Northern Norway. All inhabitants above 24 yr were invited. In total, 26 530 (75%) had their Hb analysed. RESULTS: The 2.5-97.5 percentile of Hb was 129-166 and 114-152 g/L for all men and women, respectively. In men, mean Hb decreased from 148 to 137 g/L between 55-64 and 85+ yr. In women, mean Hb increased from 132 to 137 g/L between 35-44 and 65-74 yr and then decreased to 131 g/L among the oldest. Using the WHO criteria for anaemia (Hb: <130 and <120 g/L, men and women respectively), the prevalence of anaemia in men increased with age from 0.6% aged 25-34 to 29.6% aged 85+. For women, the prevalence of anaemia varied from 9.1%, 2.2% and 16.5% in the age groups of 35-44, 55-64 and 85+ yr, respectively. The WHO criteria gave a two to three times higher prevalence of anaemia compared with the 2.5 percentile of Hb in women, but the difference was small in men. Poor self-rated health was not associated with low values of Hb in women. In men, there was an association in some age groups. CONCLUSION: The WHO criteria for anaemia and the 2.5 percentile for Hb corresponded well for men, but not for women. The WHO criteria of anaemia may result in medicalization of healthy women.

Bone marrow hyaluronan distribution in patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) is a clonal disorder characterized by abnormal proliferation of myeloid cell precursors. Research has mainly focused on the cellular events, but the bone marrow matrix has attracted minor interest. In this study bone marrow biopsies were obtained from 35 newly diagnosed AML patients. The bone marrows were analyzed regarding the occurrence and distribution of hyaluronan (HYA) and reticulin fibers (type III collagen). The bone marrow sections were analyzed histochemically and compared with bone marrows from 30 healthy controls. The HYA staining was significantly stronger in the AML patients compared with the controls. Only one patient demonstrated abnormal reticulin staining score, but in the group of patients with antecedent myelodysplastic syndrome (MDS), the reticulin staining score was significantly higher compared with the patients with de novo AML. There was a significant correlation between the HYA staining and reticulin staining scores in the AML patients as was seen in the control group.