Prognostic Significance of Bone‐Marrow Patterns in Chronic Lymphocytic Leukaemia

Rozmán, C; Hernández-Nieto, L; Montserrat, Emili; Brugués, R

doi:10.1111/j.1365-2141.1981.tb02681.x

Cited by 76 publications

(23 citation statements)

References 21 publications

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“…18 Bone marrow histologic pattern (diffuse involvement versus all other patterns) is an accepted adjunct to staging in CLL and has the potential to identify patients with greater likelihood of progression and shorter survival independent of stage. 19,20 Over the past 30 years, significant changes in the pattern of diagnosis of CLL have occurred with a shift from patients presenting with bulky nodes and cytopenias, to the detection of asymptomatic individuals identified by an elevated lymphocyte count on automated differential blood counts. 4 With the use of immunophenotyping and flow cytometry, the diagnosis of CLL has also become more precise.…”

Section: Stagingmentioning

confidence: 99%

Prognosis at diagnosis: integrating molecular biologic insights into clinical practice for patients with CLL

Shanafelt

Geyer

Kay

2004

Blood

217

165

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Heterogeneity in the clinical behavior of patients with chronic lymphocytic leukemia (CLL) makes it difficult for physicians to accurately identify which patients may benefit from an early or more aggressive treatment strategy and to provide patients with relevant prognostic information. Given the potential efficacy of newer therapies and the desire to treat patients at "optimum" times, it is more important than ever to develop sensitive stratification parameters to identify patients with poor prognosis. The evolution of risk stratification models has advanced from clinical staging and use of basic laboratory parameters to include relevant biologic and genetic features. This article will review the dramatic progress in prognostication for CLL and will propose statistical modeling techniques to evaluate the utility of these new measures in predictive models to help determine the optimal combination of markers to improve prognostication for individual patients. This discussion will also elaborate which markers and tools should be used The B-cell malignancies share a common cell lineage but a wide range of clinical, laboratory, molecular, and genetic features. Once grouped together as "subtypes" under the broad term of nonHodgkin lymphoma, the classification systems for these diseases have gone through extensive refinement to better distinguish their clinical and biologic characteristics. 1,2 Traditional teaching labeled diseases that were fatal in weeks to months if untreated as "aggressive" and those that progressed over months to years as "indolent."Through a major, collaborative, international effort, the World Health Organization (WHO) published a consensus classification system that distinguished lymphoid disorders on the basis of a combination of clinical syndromes, morphology, immunophenotype, and genetic features. 2 The WHO classification added the concept that each disorder represented a separate and distinct disease with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma grouped into a single entity (CLL). 2 Although this categorization no longer distinguishes these diseases as indolent or aggressive, the low-grade B-cell disorders are still evaluated along these lines. 3 These disorders are often considered chronic diseases of the elderly, and patients are thought likely to die of unrelated causes. These assumptions are incorrect and, to a certain extent, have hampered progress in this field.For CLL, the median age of diagnosis is 65 to 68 years old. 4 Some patients experience a slowly progressive clinical course, but most will eventually progress and have fatal outcomes. 4,5 Importantly, significant subsets of patients with early stage CLL become active, 4,[6][7][8] are refractory to treatment, 7 experience infectious or autoimmune complications, and have more rapidly fatal outcomes than anticipated.This clinical heterogeneity emphasizes the problem of considering CLL indolent and, in the era of more efficacious therapy, highlights the need to improve our ability to identify patients wit...

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Section: Stagingmentioning

confidence: 99%

Prognosis at diagnosis: integrating molecular biologic insights into clinical practice for patients with CLL

Shanafelt

Geyer

Kay

2004

Blood

217

165

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“…Distributions of our pa tients into the three clinical stages [2], disclosed a higher enzyme level in stage C patients which was sta tistically significant when compared to stage A pa tients. In addition, comparison of the enzyme activity among groups classified according to the BM histol ogy of the disease disclosed that in the diffuse pattern, which defines a group of patients with worse progno sis [3,4], the poly(A)-polymerase activity was signifi cantly higher (twice as high) than the enzyme levels in the other patterns of BM involvement. A possible role of poly(A)-polymerase as a prognostic biochemical marker in patients with B-CLL was also suggested when the enzyme activity was compared between pa tients needing no therapy and those who required a therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Pattern o f BM Infiltration. Four patterns of BM infiltration were recognized [3,4). A nodular pattern was found in 2 patients, an interstitial in 15, a mixed (nodular and interstitial) in 8 and a dif fuse pattern in 15 patients.…”

Section: Patientsmentioning

confidence: 96%

“…Factors known to predict the clinical evolution and course of CLL are the extent of the disease [1,2], the pattern of bone marrow (BM) infiltration [3,4] and the percentage of prolymphocytes in the circula tion [5,6]. Factors also reflecting its prognosis are the proliferation rate of the leukemic clone, DNA synthe sis, percentage of T lymphocytes in the blood, pres ence and quantity of immunoglobulin on the lympho cyte surface and the serum immunoglobulin level [7][8][9][10], Recent information on the biochemistry of the lymphocytes in chronic lymphocytic leukemia of the B cell type indicates a heterogeneity in the rate of pro tein synthesis, independent of the lymphocyte mor phology [10], and in the poly(A)-polymerase activity levels [11,12].…”

Section: Introductionmentioning

confidence: 99%

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Poly(A)-Polymerase Activity in Chronic Lymphocytic Leukemia of the B Cell Type

Pangalis

Trangas²,

Papanastasiou

et al. 1985

Acta Haematol

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Poly(A)-polymerase enzymic activity was biochemically determined in lymphocytic extracts from 40 patients with chronic lymphocytic leukemia of the B cell type. The enzymic activities of patients with stage A, B and C disease were (U/mg of protein): 4.9 ± 5.5, 12.5 ± 7.5 and 20.9 ± 18.9, respectively. The difference in the enzyme level between stage A and C patients was statistically significant (p < 0.05). Comparison of the enzyme activity level in relation to the pattern of bone marrow involvement revealed that patients with a diffuse pattern of infiltration had a significantly higher enzyme level (17.9 ± 15.5 U/mg of protein) than patients with interstitial or mixed infiltration patterns (5.9 ± 6.6 and 7.9 ± 7.0 U/mg of protein; p < 0.025). Finally, patients who required treatment for their disease also had a significantly higher poly(A)-polymerase activity level (14.5 ± 13.9 U/mg of protein) than patients with stable disease (4.9 ± 5.5 U/mg of protein; p < 0.05). Our results indicate that the enzyme poly(A)-polymerase may be used as a biological marker in patients with chronic lymphocytic leukemia

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“…In reality, both systems were saying the same thing, namely that the more disease you had the worse the prognosis and if the bone marrow started to fail then the outlook was dire. It was no surprise to see the International Workshop on CLL (IWCLL) recommend that the two systems be amalgamated (IWCLL, 1981(IWCLL, , 1989 indicators have since been recognized, including lymphocyte doubling time (Montserrat et al, 1986), bone marrow histology (Rozman et al, 1984) and chromosomes (Juliusson et al, 1990).…”

Section: Clinical Stagingmentioning

confidence: 99%

Historical aspects of chronic lymphocytic leukaemia

Hamblin¹

2000

Br J Haematol

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Prognostic Significance of Bone‐Marrow Patterns in Chronic Lymphocytic Leukaemia

Cited by 76 publications

References 21 publications

Prognosis at diagnosis: integrating molecular biologic insights into clinical practice for patients with CLL

Prognosis at diagnosis: integrating molecular biologic insights into clinical practice for patients with CLL

Poly(A)-Polymerase Activity in Chronic Lymphocytic Leukemia of the B Cell Type

Historical aspects of chronic lymphocytic leukaemia

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