Significance of bone marrow reticulin fibrosis in chronic lymphocytic leukemia at diagnosis: a study of 176 patients with prognostic implications.

BACKGROUND: Bone marrow (BM) biopsies from patients with chronic lymphocytic leukemia (CLL) may show reticulin fibrosis at diagnosis, but its significance remains unclear. This study sought to assess the prognostic impact of BM reticulin fibrosis in patients with previously untreated CLL. METHODS: Data was reviewed from untreated CLL patients in the national Israel CLL database, followed during 1987 to 2012. All bone marrow biopsies were graded for reticulin fibrosis using a modified scoring system containing 4 grades (0-3), based on the European consensus report. Grade of reticulin fibrosis was correlated with overall survival (OS), outcome, and a number of well-recognized prognostic factors for CLL. RESULTS: The final cohort included 176 patients (122 males and 51 females). Median age was 63 years (range, 32-86 years) and the 5-year OS was 77.1%. Grade of BM reticulin fibrosis correlated with OS (P < .0001) and mortality (P = .001), and separated patients into 2 groups with different survival curves. Advanced reticulin fibrosis (grades 2-3) was associated with thrombocytopenia (platelet counts of < 100,000/mm(3) ) (P = .025), anemia (P = .018), elevated ß2-microglobulin < 4000 µg/mL (P = .048), and the presence of 11q deletion (P = .0015). CONCLUSIONS: There was a significant correlation between poor survival and grade of BM reticulin fibrosis. This staining procedure is easy to perform and can readily be added routinely when examining BM biopsies in CLL, because the findings do have prognostic implications.

Presenting features and outcome of chronic lymphocytic leukemia patients diagnosed at age 80 years or more. An ICLLSG study.

Although the incidence of chronic lymphocytic leukemia (CLL) increases exponentially with age, data on patients 80 years or older at diagnosis are sparse. The records of patients diagnosed with CLL at age ≥80 years at seven medical centers in Israel during 1979-2009 were reviewed. Patients included 118 men and 96 women with a mean age of 84 years (range 80-94). Diagnosis was established in 56.5% due to routine blood count; 56% had Rai stage 0 disease and 25% of the patients received treatment. By June 2010, 72% had died. Mean survival was 67.7 months (median 56±5.4 months) and 5-year survival rate 47.2±3.6%. On univariate analysis, factors associated with better survival were age <84 years (p=0.002), early Rai and Binet stages (p=0.023, 0.003), low white blood cell count at time of diagnosis (p=0.015), low ß2 microglobulin level (p=0.006), diagnosis by routine blood test (p<0.001), and low CD38 level (p=0.036). Multivariate analysis using Cox regression revealed that younger age, low white cell count, and diagnosis by routine blood test were independent predictors of good prognosis (hazards ratios 1.8, 1.6, and 1.9, respectively). Patients diagnosed with CLL at age ≥80 years may expect to live a long life. This study identifies several factors predicting good prognosis which are easy to obtain.

Clinical and immunologic aspects of B chronic lymphocytic leukemia associated with autoimmune disorders.

BACKGROUND: Autoimmune disorders often develop during the course of B chronic lymphocytic leukemia. The source of the autoantibodies is still uncertain: either uncontrolled production of the malignant B cells or disturbances of the residual normal B and T cells involved in the immune system. OBJECTIVES: To evaluate immunologic parameters in B-CLL associated with autoimmune disorders. As a hypothesis we postulated that in those cases, the malignant B cells might disclose an activated phenotype pattern leading to the production of autoantibodies. METHODS: In the Registry of the Israel Study Group on CLL that includes 964 patients, we found 115 cases showing a single or a complex of autoimmune disorders. We evaluated the lymphocyte morphology, immunoglobulin G and beta-2-microglobulin serum levels and positivity of the CD38 and FMC7 markers, and compared these values with those of a matched CLL population without autoimmune disorder. RESULTS: The main autoimmune disorders encountered were autoimmune hemolytic anemia (55 patients), Evan's syndrome (n=7), Hashimoto's thyroiditis (n=15), vasculitis (n=5) and rheumatoid arthritis (n=4). We found atypical prolymphocytic morphology in 22%, high expression of the activation antigens CD38 and/or FMC7 in 30%, and high level of immunoglobulin G (> 1000 mg/dl) and beta-2-microglobulin in 57% and 78% respectively. When compared with a matched CLL population without an autoimmune disorder, these values were statistically significant. CONCLUSIONS: Our data, which show activated lymphocyte morphology, high levels of IgG and beta-2-microglobulin, and increased expression of CD38 and/or FMC7 in a significant number of cases, suggest that some degree of activation of B cells may lead to the occurrence of an autoimmune disorder in CLL.

Microangiopathic Anemia of Acute Brucellosis - is it a True TTP?

Thrombotic thrombocytopenic purpura (TTP) is a severe disease, potentially fatal, if not diagnosed and treated promptly. TTP is clinically characterized by the pentad of thrombocytopenia, Coombs-negative hemolytic anemia, fever, renal abnormalities and neurological disturbances. Advances in recent years have delineated the molecular mechanisms of acquired and hereditary TTP.Many infectious organisms have been reported to be associated with TTP, especially mycoplasma, but few cases of Brucella infection associated with thrombotic microangiopathy have been reported.We describe a young woman who presented with TTP after acute infection with both Brucella melitensis and Brucella abortus. The patient completely recovered following aggressive therapy with plasmapharesis, high-dose corticosteroids and appropriate antimicrobial therapy.Since measurement of ADAMTS13 activity and neutralizing antibodies is now available, and none of the reported cases of brucellosis with thrombotic microangiopathy (including the present report) were tested, for better understanding of this rare association, we recommend this work-up in future cases.